A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane.
An intrinsic defect of erythrocytes inherited as an autosomal dominant trait. The erythrocytes assume an oval or elliptical shape.
A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Erythrocyte-related isoforms of ankyrin attach the SPECTRIN cytoskeleton to a transmembrane protein (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE) in the erythrocyte plasma membrane. Brain-related isoforms of ankyrin also exist.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
A group of familial congenital hemolytic anemias characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. The erythrocytes have increased osmotic fragility and are abnormally permeable to sodium ions.
Hemolytic anemia due to various intrinsic defects of the erythrocyte.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Oxygen-carrying RED BLOOD CELLS in mammalian blood that are abnormal in structure or function.
Ability of ERYTHROCYTES to change shape as they pass through narrow spaces, such as the microvasculature.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC
Small, abnormal spherical red blood cells with more than the normal amount of hemoglobin.
A major integral transmembrane protein of the ERYTHROCYTE MEMBRANE. It is the anion exchanger responsible for electroneutral transporting in CHLORIDE IONS in exchange of BICARBONATE IONS allowing CO2 uptake and transport from tissues to lungs by the red blood cells. Genetic mutations that result in a loss of the protein function have been associated with type 4 HEREDITARY SPHEROCYTOSIS.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.

A human beta-spectrin gene promoter directs high level expression in erythroid but not muscle or neural cells. (1/1097)

beta-Spectrin is an erythrocyte membrane protein that is defective in many patients with abnormalities of red blood cell shape including hereditary spherocytosis and elliptocytosis. It is expressed not only in erythroid tissues but also in muscle and brain. We wished to determine the regulatory elements that determine the tissue-specific expression of the beta-spectrin gene. We mapped the 5'-end of the beta-spectrin erythroid cDNA and cloned the 5'-flanking genomic DNA containing the putative beta-spectrin gene promoter. Using transfection of promoter/reporter plasmids in human tissue culture cell lines, in vitro DNase I footprinting analyses, and gel mobility shift assays, a beta-spectrin gene erythroid promoter with two binding sites for GATA-1 and one site for CACCC-related proteins was identified. All three binding sites were required for full promoter activity; one of the GATA-1 motifs and the CACCC-binding motif were essential for activity. The beta-spectrin gene promoter was able to be transactivated in heterologous cells by forced expression of GATA-1. In transgenic mice, a reporter gene directed by the beta-spectrin promoter was expressed in erythroid tissues at all stages of development. Only weak expression of the reporter gene was detected in muscle and brain tissue, suggesting that additional regulatory elements are required for high level expression of the beta-spectrin gene in these tissues.  (+info)

Calculation of a Gap restoration in the membrane skeleton of the red blood cell: possible role for myosin II in local repair. (2/1097)

Human red blood cells contain all of the elements involved in the formation of nonmuscle actomyosin II complexes (V. M. Fowler. 1986. J. Cell. Biochem. 31:1-9; 1996. Curr. Opin. Cell Biol. 8:86-96). No clear function has yet been attributed to these complexes. Using a mathematical model for the structure of the red blood cell spectrin skeleton (M. J. Saxton. 1992. J. Theor. Biol. 155:517-536), we have explored a possible role for myosin II bipolar minifilaments in the restoration of the membrane skeleton, which may be locally damaged by major mechanical or chemical stress. We propose that the establishment of stable links between distant antiparallel actin protofilaments after a local myosin II activation may initiate the repair of the disrupted area. We show that it is possible to define conditions in which the calculated number of myosin II minifilaments bound to actin protofilaments is consistent with the estimated number of myosin II minifilaments present in the red blood cells. A clear restoration effect can be observed when more than 50% of the spectrin polymers of a defined area are disrupted. It corresponds to a significant increase in the spectrin density in the protein free region of the membrane. This may be involved in a more complex repair process of the red blood cell membrane, which includes the vesiculation of the bilayer and the compaction of the disassembled spectrin network.  (+info)

Electric birefringence of recombinant spectrin segments 14, 14-15, 14-16, and 14-17 from Drosophila alpha-spectrin. (3/1097)

Members of the spectrin protein family can be found in many different cells and organisms. In all cases studied, the major functional role of these proteins is believed to be structural rather than enzymatic. All spectrin proteins are highly elongated and consist mainly of homologous repeats that constitute rigid segments connected in tandem. It is commonly believed that the details of the spectrin function depend critically on the flexibility of the links between the segments. Here we report on a work addressing this question by studying the transient electric birefringence of recombinant spectrin fragments consisting of segments 14, 14-15, 14-16, and 14-17, respectively, from Drosophila alpha-spectrin. Transient electric birefringence depends sharply on both molecular length and flexibility. We found that the birefringence relaxation time of segment 14 measured at 4 degrees C, but scaled to what is expected at 20 degrees C, equals 16 ns (+/-15%) at pH 7.5 and ionic strength 6 mM. This is consistent with this single segment being rigid, 5 nm long and having an axial ratio equal to about two. Under the same conditions, segments 14-15, 14-16 and 14-17 show relaxation times of 45, 39 and 164 ns (all +/-20%), respectively, scaled to what is expected at 20 degrees C. When the temperature is increased to 37 degrees C the main relaxation time for each of these multisegment fragments, scaled to what is expected at 20 degrees C, increased to 46, 80, and 229 ns (all +/-20%), respectively. When the ionic strength and the Debye shielding is low, the dynamics of these short fragments even at physiological temperature is nearly the same as for fully extended weakly bending rods with the same lengths and axial ratios. When the ionic strength is increased to 85 mM, the main relaxation time for each of these multisegment fragments is reduced 20-50% which suggests that at physiological salt and temperature conditions the links in 2-4-segment-long fragments exhibit significant thermally induced flexing. Provided that the recombinant spectrin fragments can serve as a model for native spectrin, this implies that, at physiological conditions, the overall conformational dynamics of a native spectrin protein containing 20-40 segments equals that of a flexible polymer.  (+info)

Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. (4/1097)

We used immunofluorescence techniques and confocal imaging to study the organization of the membrane skeleton of skeletal muscle fibers of mdx mice, which lack dystrophin. beta-Spectrin is normally found at the sarcolemma in costameres, a rectilinear array of longitudinal strands and elements overlying Z and M lines. However, in the skeletal muscle of mdx mice, beta-spectrin tends to be absent from the sarcolemma over M lines and the longitudinal strands may be disrupted or missing. Other proteins of the membrane and associated cytoskeleton, including syntrophin, beta-dystroglycan, vinculin, and Na,K-ATPase are also concentrated in costameres, in control myofibers, and mdx muscle. They also distribute into the same altered sarcolemmal arrays that contain beta-spectrin. Utrophin, which is expressed in mdx muscle, also codistributes with beta-spectrin at the mutant sarcolemma. By contrast, the distribution of structural and intracellular membrane proteins, including alpha-actinin, the Ca-ATPase and dihydropyridine receptors, is not affected, even at sites close to the sarcolemma. Our results suggest that in myofibers of the mdx mouse, the membrane- associated cytoskeleton, but not the nearby myoplasm, undergoes widespread coordinated changes in organization. These changes may contribute to the fragility of the sarcolemma of dystrophic muscle.  (+info)

Effect of fever-like whole-body hyperthermia on lymphocyte spectrin distribution, protein kinase C activity, and uropod formation. (5/1097)

Regional inflammation and systemic fever are hallmarks of host immune responses to pathogenic stimuli. Although the thermal element of fever is thought to enhance the activity of immune effector cells, it is unclear what the precise role of increased body temperatures is on the activation state and effector functions of lymphocytes. We report here that mild, fever-like whole body hyperthermia (WBH) treatment of mice results in a distinct increase in the numbers of tissue lymphocytes with polarized spectrin cytoskeletons and uropods, as visualized in situ. WBH also induces a coincident reorganization of protein kinase C (PKC) isozymes and increased PKC activity within T cells. These hyperthermia-induced cellular alterations are nearly identical with the previously described effects of Ag- and mitogen-induced activation on lymphocyte spectrin and PKC. Immunoprecipitation studies combined with dual staining and protein overlay assays confirmed the association of PKC beta and PKC theta with spectrin following its reorganization. The receptor for activated C kinase-1 was also found to associate with the spectrin-based cytoskeleton. Furthermore, all these molecules (spectrin, PKC beta, PKC theta, and receptor for activated C kinase-1) cotranslocate to the uropod. Enhanced intracellular spectrin phosphorylation upon WBH treatment of lymphocytes was also found and could be blocked by the PKC inhibitor bisindolylmaleimide I (GF109203X). These data suggest that the thermal element of fever, as mimicked by these studies, can modulate critical steps in the signal transduction pathways necessary for effective lymphocyte activation and function. Further work is needed to determine the cellular target(s) that transduces the signaling pathway(s) induced by hyperthermia.  (+info)

Interaction of the DNA-binding antitumor antibiotics, chromomycin and mithramycin with erythroid spectrin. (6/1097)

The aureolic acid group of antitumor antibiotics, chromomycin A3 and mithramycin, are well established as transcription inhibitors, which bind reversibly to DNA at and above physiological pH, in the presence of divalent metal ions such as Mg2+. As part of our broad objective to elucidate their intracellular mode of action, other than association with DNA, we studied their interactions with the erythrocyte cytoskeletal protein, spectrin, in the absence and presence of magnesium. Different spectroscopic studies, such as absorbance, fluorescence and CD, have shown that both free chromomycin and mithramycin and their Mg2+ complexes bind to spectrin with an affinity higher than that reported for DNA. The affinity constants for the association of chromomycin and mithramycin (or their Mg2+ complexes) with spectrin are comparable with those for the association of spectrin with other cytoskeletal proteins, for example F-actin, ankyrin, protein 4.1, etc. The nature of the binding of the two antibiotics to spectrin is different. The mode of binding of the antibiotics with spectrin also changes in the presence of Mg2+. The interaction leads to a change in the tertiary structure of the protein. The relevance of the results to our understanding of the mode of action of the antibiotics is discussed.  (+info)

Alteration of alpha-spectrin ubiquitination due to age-dependent changes in the erythrocyte membrane. (7/1097)

Mammalian red blood cell alpha-spectrin is ubiquitinated in vitro and in vivo [Corsi, D., Galluzzi, L., Crinelli, R., Magnani, M. (1995) J. Biol. Chem. 270, 8928-8935]. This process shows a cell age-dependent decrease, with senescent red blood cells having approximately one third of the amount of ubiquitinated alpha-spectrin found in young cells. In-vitro ubiquitination of alpha-spectrin was dependent on the source of the red cell membranes (those from older cells are less susceptible to ubiquitination than those from younger cells), on the source of ubiquitin-conjugating enzymes (those from older cells catalyze the process at a reduced rate compared to those from younger cells) and on the ubiquitin isopeptidase activity (which decreases during red cell ageing). However, once alpha-spectrin has been extracted from the membranes of young or old red blood cells, it is susceptible to ubiquitination to a similar extent regardless of source. This suggests that it is the membrane architecture, and not spectrin itself, that is responsible for the age-dependent decline in ubiquitination. Furthermore, spectrin oligomers, tetramers and dimers are also equally susceptible to ubiquitination. As spectrin ubiquitination occurs on domains alphaIII and alphaV of alpha-spectrin, and domain alphaV contains the nucleation site for the association of the alpha- and beta-spectrin chains, alterations in ubiquitination during red cell ageing could affect the stability and deformability of the erythrocyte membrane.  (+info)

Mild spherocytosis and altered red cell ion transport in protein 4. 2-null mice. (8/1097)

Protein 4.2 is a major component of the red blood cell (RBC) membrane skeleton. We used targeted mutagenesis in embryonic stem (ES) cells to elucidate protein 4.2 functions in vivo. Protein 4. 2-null (4.2(-/-)) mice have mild hereditary spherocytosis (HS). Scanning electron microscopy and ektacytometry confirm loss of membrane surface in 4.2(-/-) RBCs. The membrane skeleton architecture is intact, and the spectrin and ankyrin content of 4. 2(-/-) RBCs are normal. Band 3 and band 3-mediated anion transport are decreased. Protein 4.2(-/-) RBCs show altered cation content (increased K+/decreased Na+)resulting in dehydration. The passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl cotransporters, the Na/H exchanger, and the Gardos channel in 4. 2(-/-) RBCs are significantly increased. Protein 4.2(-/-) RBCs demonstrate an abnormal regulation of cation transport by cell volume. Cell shrinkage induces a greater activation of Na/H exchange and Na-K-2Cl cotransport in 4.2(-/-) RBCs compared with controls. The increased passive Na+ permeability of 4.2(-/-) RBCs is also dependent on cell shrinkage. We conclude that protein 4.2 is important in the maintenance of normal surface area in RBCs and for normal RBC cation transport.  (+info)

Spectrin is a type of cytoskeletal protein that is responsible for providing structural support and maintaining the shape of red blood cells (erythrocytes). It is a key component of the erythrocyte membrane skeleton, which provides flexibility and resilience to these cells, allowing them to deform and change shape as they pass through narrow capillaries. Spectrin forms a network of fibers just beneath the cell membrane, along with other proteins such as actin, band 4.1, and band 3. Mutations in spectrin genes can lead to various blood disorders, including hereditary spherocytosis and hemolytic anemia.

Hereditary elliptocytosis is a genetic condition characterized by the presence of abnormally shaped red blood cells (RBCs), which are often oval or elliptical in shape instead of the typical biconcave disc shape. This condition is caused by mutations in genes that encode proteins responsible for maintaining the stability and flexibility of RBCs, such as spectrin and ankyrin.

There are several types of hereditary elliptocytosis, including:

1. Type 1 Hereditary Elliptocytosis (HE): This is the most common form and is usually a mild condition with few or no symptoms. It is caused by mutations in the spectrin gene.
2. Type 2 Hereditary Elliptocytosis (HE): This form is less common and can be more severe than type 1, with symptoms such as anemia, fatigue, and jaundice. It is caused by mutations in the gene that encodes the protein ankyrin.
3. Spherocytic Elliptocytosis (SE): This is a rare form of hereditary elliptocytosis that combines features of both hereditary elliptocytosis and hereditary spherocytosis, another genetic RBC disorder. SE is caused by mutations in genes that encode spectrin or ankyrin.

In general, people with hereditary elliptocytosis have few or no symptoms and do not require treatment. However, in some cases, severe hemolysis (breakdown of RBCs) can occur, leading to anemia, jaundice, gallstones, and other complications. In these cases, treatment may be necessary to manage the symptoms and prevent further complications.

Ankyrins are a group of proteins that play a crucial role in the organization and function of the plasma membrane in cells. They are characterized by the presence of ankyrin repeats, which are structural motifs that mediate protein-protein interactions. Ankyrins serve as adaptor proteins that link various membrane proteins to the underlying cytoskeleton, providing stability and organization to the plasma membrane.

There are several isoforms of ankyrins, including ankyrin-R, ankyrin-B, and ankyrin-G, which differ in their expression patterns and functions. Ankyrin-R is primarily expressed in neurons and is involved in the localization and clustering of ion channels and transporters at specialized domains of the plasma membrane, such as nodes of Ranvier and axon initial segments. Ankyrin-B is widely expressed and has been implicated in the regulation of various cellular processes, including cell adhesion, signaling, and trafficking. Ankyrin-G is predominantly found in muscle and neuronal tissues and plays a role in the organization of ion channels and transporters at the sarcolemma and nodes of Ranvier.

Mutations in ankyrin genes have been associated with various human diseases, including neurological disorders, cardiac arrhythmias, and hemolytic anemia.

An erythrocyte, also known as a red blood cell, is a type of cell that circulates in the blood and is responsible for transporting oxygen throughout the body. The erythrocyte membrane refers to the thin, flexible barrier that surrounds the erythrocyte and helps to maintain its shape and stability.

The erythrocyte membrane is composed of a lipid bilayer, which contains various proteins and carbohydrates. These components help to regulate the movement of molecules into and out of the erythrocyte, as well as provide structural support and protection for the cell.

The main lipids found in the erythrocyte membrane are phospholipids and cholesterol, which are arranged in a bilayer structure with the hydrophilic (water-loving) heads facing outward and the hydrophobic (water-fearing) tails facing inward. This arrangement helps to maintain the integrity of the membrane and prevent the leakage of cellular components.

The proteins found in the erythrocyte membrane include integral proteins, which span the entire width of the membrane, and peripheral proteins, which are attached to the inner or outer surface of the membrane. These proteins play a variety of roles, such as transporting molecules across the membrane, maintaining the shape of the erythrocyte, and interacting with other cells and proteins in the body.

The carbohydrates found in the erythrocyte membrane are attached to the outer surface of the membrane and help to identify the cell as part of the body's own immune system. They also play a role in cell-cell recognition and adhesion.

Overall, the erythrocyte membrane is a complex and dynamic structure that plays a critical role in maintaining the function and integrity of red blood cells.

Hereditary Spherocytosis is a genetic disorder that affects the red blood cells (RBCs) causing them to take on a spherical shape instead of their normal biconcave disc shape. This occurs due to mutations in the genes responsible for the proteins that maintain the structure and flexibility of RBCs, such as ankyrin, band 3, spectrin, and protein 4.2.

The abnormally shaped RBCs are fragile and prone to hemolysis (premature destruction), which can lead to anemia, jaundice, and gallstones. Symptoms can vary from mild to severe and may include fatigue, weakness, shortness of breath, and a yellowing of the skin and eyes (jaundice). Diagnosis is typically made through a combination of family history, physical examination, complete blood count (CBC), and specialized tests such as osmotic fragility test, eosin-5'-maleimide binding test, or direct antiglobulin test. Treatment may include monitoring, supplementation with folic acid, and in severe cases, splenectomy (surgical removal of the spleen) to reduce RBC destruction.

Hemolytic anemia, congenital is a type of anemia that is present at birth and characterized by the abnormal breakdown (hemolysis) of red blood cells. This can occur due to various genetic defects that affect the structure or function of the red blood cells, making them more susceptible to damage and destruction.

There are several types of congenital hemolytic anemias, including:

1. Congenital spherocytosis: A condition caused by mutations in genes that affect the shape and stability of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
2. G6PD deficiency: A genetic disorder that affects the enzyme glucose-6-phosphate dehydrogenase (G6PD), which is essential for protecting red blood cells from damage. People with this condition have low levels of G6PD, making their red blood cells more susceptible to hemolysis when exposed to certain triggers such as infections or certain medications.
3. Hereditary elliptocytosis: A condition caused by mutations in genes that affect the structure and flexibility of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
4. Pyruvate kinase deficiency: A rare genetic disorder that affects an enzyme called pyruvate kinase, which is essential for the production of energy in red blood cells. People with this condition have low levels of pyruvate kinase, leading to the formation of fragile and abnormally shaped red blood cells that are prone to hemolysis.

Symptoms of congenital hemolytic anemia can vary depending on the severity of the condition but may include fatigue, weakness, pale skin, jaundice, dark urine, and an enlarged spleen. Treatment may involve blood transfusions, medications to manage symptoms, and in some cases, surgery to remove the spleen.

Erythrocytes, also known as red blood cells (RBCs), are the most common type of blood cell in circulating blood in mammals. They are responsible for transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

Erythrocytes are formed in the bone marrow and have a biconcave shape, which allows them to fold and bend easily as they pass through narrow blood vessels. They do not have a nucleus or mitochondria, which makes them more flexible but also limits their ability to reproduce or repair themselves.

In humans, erythrocytes are typically disc-shaped and measure about 7 micrometers in diameter. They contain the protein hemoglobin, which binds to oxygen and gives blood its red color. The lifespan of an erythrocyte is approximately 120 days, after which it is broken down in the liver and spleen.

Abnormalities in erythrocyte count or function can lead to various medical conditions, such as anemia, polycythemia, and sickle cell disease.

Abnormal erythrocytes refer to red blood cells that have an abnormal shape, size, or other characteristics. This can include various types of abnormalities such as:

1. Anisocytosis: Variation in the size of erythrocytes.
2. Poikilocytosis: Variation in the shape of erythrocytes, including but not limited to teardrop-shaped cells (dacrocytes), crescent-shaped cells (sickle cells), and spherical cells (spherocytes).
3. Anemia: A decrease in the total number of erythrocytes or a reduction in hemoglobin concentration, which can result from various underlying conditions such as iron deficiency, chronic disease, or blood loss.
4. Hemoglobinopathies: Abnormalities in the structure or function of hemoglobin, the protein responsible for carrying oxygen in erythrocytes, such as sickle cell anemia and thalassemia.
5. Inclusion bodies: Abnormal structures within erythrocytes, such as Heinz bodies (denatured hemoglobin) or Howell-Jolly bodies (nuclear remnants).

These abnormalities can be detected through a complete blood count (CBC) and peripheral blood smear examination. The presence of abnormal erythrocytes may indicate an underlying medical condition, and further evaluation is often necessary to determine the cause and appropriate treatment.

Erythrocyte deformability refers to the ability of red blood cells (erythrocytes) to change shape and bend without rupturing, which is crucial for their efficient movement through narrow blood vessels. This deformability is influenced by several factors including the cell membrane structure, hemoglobin concentration, and intracellular viscosity. A decrease in erythrocyte deformability can negatively impact blood flow and oxygen delivery to tissues, potentially contributing to various pathological conditions such as sickle cell disease, diabetes, and cardiovascular diseases.

Membrane proteins are a type of protein that are embedded in the lipid bilayer of biological membranes, such as the plasma membrane of cells or the inner membrane of mitochondria. These proteins play crucial roles in various cellular processes, including:

1. Cell-cell recognition and signaling
2. Transport of molecules across the membrane (selective permeability)
3. Enzymatic reactions at the membrane surface
4. Energy transduction and conversion
5. Mechanosensation and signal transduction

Membrane proteins can be classified into two main categories: integral membrane proteins, which are permanently associated with the lipid bilayer, and peripheral membrane proteins, which are temporarily or loosely attached to the membrane surface. Integral membrane proteins can further be divided into three subcategories based on their topology:

1. Transmembrane proteins, which span the entire width of the lipid bilayer with one or more alpha-helices or beta-barrels.
2. Lipid-anchored proteins, which are covalently attached to lipids in the membrane via a glycosylphosphatidylinositol (GPI) anchor or other lipid modifications.
3. Monotopic proteins, which are partially embedded in the membrane and have one or more domains exposed to either side of the bilayer.

Membrane proteins are essential for maintaining cellular homeostasis and are targets for various therapeutic interventions, including drug development and gene therapy. However, their structural complexity and hydrophobicity make them challenging to study using traditional biochemical methods, requiring specialized techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and single-particle cryo-electron microscopy (cryo-EM).

The cytoskeleton is a complex network of various protein filaments that provides structural support, shape, and stability to the cell. It plays a crucial role in maintaining cellular integrity, intracellular organization, and enabling cell movement. The cytoskeleton is composed of three major types of protein fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. These filaments work together to provide mechanical support, participate in cell division, intracellular transport, and help maintain the cell's architecture. The dynamic nature of the cytoskeleton allows cells to adapt to changing environmental conditions and respond to various stimuli.

Macromolecular substances, also known as macromolecules, are large, complex molecules made up of repeating subunits called monomers. These substances are formed through polymerization, a process in which many small molecules combine to form a larger one. Macromolecular substances can be naturally occurring, such as proteins, DNA, and carbohydrates, or synthetic, such as plastics and synthetic fibers.

In the context of medicine, macromolecular substances are often used in the development of drugs and medical devices. For example, some drugs are designed to bind to specific macromolecules in the body, such as proteins or DNA, in order to alter their function and produce a therapeutic effect. Additionally, macromolecular substances may be used in the creation of medical implants, such as artificial joints and heart valves, due to their strength and durability.

It is important for healthcare professionals to have an understanding of macromolecular substances and how they function in the body, as this knowledge can inform the development and use of medical treatments.

Microfilament proteins are a type of structural protein that form part of the cytoskeleton in eukaryotic cells. They are made up of actin monomers, which polymerize to form long, thin filaments. These filaments are involved in various cellular processes such as muscle contraction, cell division, and cell motility. Microfilament proteins also interact with other cytoskeletal components like intermediate filaments and microtubules to maintain the overall shape and integrity of the cell. Additionally, they play a crucial role in the formation of cell-cell junctions and cell-matrix adhesions, which are essential for tissue structure and function.

Cytoskeletal proteins are a type of structural proteins that form the cytoskeleton, which is the internal framework of cells. The cytoskeleton provides shape, support, and structure to the cell, and plays important roles in cell division, intracellular transport, and maintenance of cell shape and integrity.

There are three main types of cytoskeletal proteins: actin filaments, intermediate filaments, and microtubules. Actin filaments are thin, rod-like structures that are involved in muscle contraction, cell motility, and cell division. Intermediate filaments are thicker than actin filaments and provide structural support to the cell. Microtubules are hollow tubes that are involved in intracellular transport, cell division, and maintenance of cell shape.

Cytoskeletal proteins are composed of different subunits that polymerize to form filamentous structures. These proteins can be dynamically assembled and disassembled, allowing cells to change their shape and move. Mutations in cytoskeletal proteins have been linked to various human diseases, including cancer, neurological disorders, and muscular dystrophies.

Actin is a type of protein that forms part of the contractile apparatus in muscle cells, and is also found in various other cell types. It is a globular protein that polymerizes to form long filaments, which are important for many cellular processes such as cell division, cell motility, and the maintenance of cell shape. In muscle cells, actin filaments interact with another type of protein called myosin to enable muscle contraction. Actins can be further divided into different subtypes, including alpha-actin, beta-actin, and gamma-actin, which have distinct functions and expression patterns in the body.

Calpains are a family of calcium-dependent cysteine proteases that play important roles in various cellular processes, including signal transduction, cell death, and remodeling of the cytoskeleton. They are present in most tissues and can be activated by an increase in intracellular calcium levels. There are at least 15 different calpain isoforms identified in humans, which are categorized into two groups based on their calcium requirements for activation: classical calpains (calpain-1 and calpain-2) and non-classical calpains (calpain-3 to calpain-15). Dysregulation of calpain activity has been implicated in several pathological conditions, such as neurodegenerative diseases, muscular dystrophies, and cancer.

Spherocytes are a type of abnormally shaped red blood cell that appear smaller and rounder than normal red blood cells (which are typically disc-shaped). This abnormal shape is caused by a loss or decrease in the central portion of the cell membrane, which leads to a reduction in surface area relative to the volume of the cell. As a result, spherocytes are less flexible and more susceptible to being destroyed or hemolysed, particularly when they pass through narrow blood vessels such as those found in the spleen. Spherocytosis is a term used to describe the condition where there is an increased number of spherocytes in the blood. This condition can be inherited or acquired and may lead to anemia, jaundice, and splenomegaly (enlarged spleen).

Anion Exchange Protein 1, Erythrocyte (AE1), also known as Band 3 protein or SLC4A1, is a transmembrane protein found in the membranes of red blood cells (erythrocytes). It plays a crucial role in maintaining the pH and bicarbonate levels of the blood by facilitating the exchange of chloride ions (Cl-) with bicarbonate ions (HCO3-) between the red blood cells and the plasma.

The anion exchange protein 1 is composed of three major domains: a cytoplasmic domain, a transmembrane domain, and an extracellular domain. The cytoplasmic domain interacts with various proteins involved in regulating the cytoskeleton of the red blood cell, while the transmembrane domain contains the ion exchange site. The extracellular domain is responsible for the interaction between red blood cells and contributes to their aggregation.

Mutations in the AE1 gene can lead to various inherited disorders, such as hereditary spherocytosis, Southeast Asian ovalocytosis, and distal renal tubular acidosis type 1. These conditions are characterized by abnormal red blood cell shapes, impaired kidney function, or both.

Blood proteins, also known as serum proteins, are a group of complex molecules present in the blood that are essential for various physiological functions. These proteins include albumin, globulins (alpha, beta, and gamma), and fibrinogen. They play crucial roles in maintaining oncotic pressure, transporting hormones, enzymes, vitamins, and minerals, providing immune defense, and contributing to blood clotting.

Albumin is the most abundant protein in the blood, accounting for about 60% of the total protein mass. It functions as a transporter of various substances, such as hormones, fatty acids, and drugs, and helps maintain oncotic pressure, which is essential for fluid balance between the blood vessels and surrounding tissues.

Globulins are divided into three main categories: alpha, beta, and gamma globulins. Alpha and beta globulins consist of transport proteins like lipoproteins, hormone-binding proteins, and enzymes. Gamma globulins, also known as immunoglobulins or antibodies, are essential for the immune system's defense against pathogens.

Fibrinogen is a protein involved in blood clotting. When an injury occurs, fibrinogen is converted into fibrin, which forms a mesh to trap platelets and form a clot, preventing excessive bleeding.

Abnormal levels of these proteins can indicate various medical conditions, such as liver or kidney disease, malnutrition, infections, inflammation, or autoimmune disorders. Blood protein levels are typically measured through laboratory tests like serum protein electrophoresis (SPE) and immunoelectrophoresis (IEP).

Similarly, spectrin plays a role in Drosophila neurons. Knock-out of α or β spectrin in D. melanogaster results in neurons that ... In animals, spectrin forms the meshwork that provides red blood cells their shape. The spectrin gene family has undergone ... Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms ... Spectrin subunits may also be cleaved by caspase family enzymes, and calpain and caspase produce different spectrin breakdown ...
The spectrin repeat forms a three-helix bundle. These conform to the rules of the heptad repeat. Spectrin repeats give rise to ... Spectrin repeats are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin, ... There are hints however, that some proteins harbouring spectrin repeats may also be flexible. This is most likely due to ... Harrison SC, Yan Y, Winograd E, Viel A, Cronin T, Branton D (1993). "Crystal structure of the repetitive segments of spectrin ...
Spectrin alpha chain, erythrocyte is a protein that in humans is encoded by the SPTA1 gene. Spectrin is an actin crosslinking ... 1992). "Spectrin Jendouba: an alpha II/31 spectrin variant that is associated with elliptocytosis and carries a mutation ... This gene is one member of a family of alpha-spectrin genes. The encoded protein is primarily composed of 22 spectrin repeats ... 1992). "A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/ ...
In molecular biology, the calmodulin-regulated spectrin-associated CKK domain (also known as the CKK domain) is a domain which ... occurs at the C-terminus of a family of eumetazoan proteins collectively defined as calmodulin-regulated spectrin-associated, ...
... , or Nesprin-3, is a Nesprin-family protein that in humans is ... "Entrez Gene: Spectrin repeat containing nuclear envelope family member 3". Retrieved 2018-05-27. Wilhelmsen K, Litjens SH, ...
"Pfam entry Spectrin". Archived from the original on 2007-09-26. Retrieved 2007-01-25. Rochat H, Martin-Eauclaire MF, eds. (2000 ...
1: Spectrin super family". Protein Prof. 2 (7): 703-800. PMID 7584474. Gimona M, Mital R (1998). "The single CH domain of ... It comprises the following groups of actin-binding domains: Actinin-type (including spectrin, fimbrin, ABP-280) Calponin-type A ...
January 2006). "Spectrin mutations cause spinocerebellar ataxia type 5". Nature Genetics. 38 (2): 184-90. doi:10.1038/ng1728. ...
Riederer BM, Routtenberg A (Aug 1999). "Can GAP-43 interact with brain spectrin?". Brain Research. Molecular Brain Research. 71 ... spectrin, palmitate, synaptophysin, amyloid and tau protein, it may be useful to think of GAP43 as an adaptor protein situated ...
Sadler, T.W. (1986). "A potential role for spectrin during neurulation". J. Embryol. 94 (1): 73-82. Retrieved 27 April 2013. ...
SEC14 and spectrin domains 1, also known as SEC14 domain and spectrin repeat-containing protein 1 and Solo, is a protein that ... "Entrez Gene: SEC14 and spectrin domains 1". Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial ...
Spectrin beta chain, brain 2 is a protein that in humans is encoded by the SPTBN2 gene. Mutations in this gene is associated ... "Entrez Gene: SPTBN2 spectrin, beta, non-erythrocytic 2". Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C (May 2001 ... Holleran EA, Ligon LA, Tokito M, Stankewich MC, Morrow JS, Holzbaur EL (2001). "beta III spectrin binds to the Arp1 subunit of ... Holleran EA, Ligon LA, Tokito M, Stankewich MC, Morrow JS, Holzbaur EL (September 2001). "beta III spectrin binds to the Arp1 ...
Li X, Bennett V (1996). "Identification of the spectrin subunit and domains required for formation of spectrin/adducin/actin ... Gardner K, Bennett V (1987). "Modulation of spectrin-actin assembly by erythrocyte adducin". Nature. 328 (6128): 359-62. ... phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, ...
Spectrin beta chain, brain 1 is a protein that in humans is encoded by the SPTBN1 gene. Spectrin is an actin crosslinking and ... "Identification of a novel C-terminal variant of beta II spectrin: two isoforms of beta II spectrin have distinct intracellular ... Chen Y, Yu P, Lu D, Tagle DA, Cai T (2002). "A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies ... "Entrez Gene: SPTBN1 spectrin, beta, non-erythrocytic 1". Neill GW, Crompton MR (September 2001). "Binding of the merlin-I ...
"Entrez Gene: Spectrin repeat containing, nuclear envelope 1". "Compute pI/Mw for SYNE1_HUMAN (Q8NF91)". ExPASy. Swiss Institute ... This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood ... a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues". J. Cell Sci. ...
Fletcher, G.C.; Elbediwy, A.; Khanal, I.; Ribeiro, P.S.; Tapon, N.; Thompson, B.J. (2010). "The Spectrin cytoskeleton regulates ...
Spectrin, beta, non-erythrocytic 4, also known as SPTBN4, is a protein that in humans is encoded by the SPTBN4 gene. Spectrin ... "betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous ... "betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous ... Tse WT, Tang J, Jin O, Korsgren C, John KM, Kung AL, Gwynn B, Peters LL, Lux SE (2001). "A new spectrin, beta IV, has a major ...
"Structure of the pleckstrin homology domain from beta-spectrin". Nature. 369 (6482): 675-7. Bibcode:1994Natur.369..675M. doi: ...
Spectrin, beta, non-erythrocytic 5 also known as SPTBN5 is a protein that in humans is encoded by the SPTBN5 gene. SPTBN5 ... Based on these structural features it is thought that SPTBN5 is likely to form heterodimers and oligomers with alpha-spectrin ... Odell AF, Van Helden DF, Scott JL (2008). "The spectrin cytoskeleton influences the surface expression and activation of human ... Stabach PR, Morrow JS (July 2000). "Identification and characterization of beta V spectrin, a mammalian ortholog of Drosophila ...
1996) α-spectrin is required for germline cell division and differentiation in the Drosophila ovary. Development 122: 3959-3968 ... Intercellular junctions Gametogenesis Spectrin Cyclin Telfer, W. H. 1975. Development and physiology of the oocyte-nurse cell ... been identified in Xenopus laevis oogenesis by electron microscopy and immunostaining for fusome components such as spectrin ...
"Structure of the pleckstrin homology domain from beta-spectrin". Nature. 369 (6482): 675-7. Bibcode:1994Natur.369..675M. doi: ...
Spectrin helps to create a network by cross-linked actin filaments. The proportions of spectrin and actin vary with cell type. ... Spectrin proteins and actin microfilaments are attached to transmembrane proteins by attachment proteins between them and the ... The cell cortex is attached to the inner cytosolic face of the plasma membrane in cells where the spectrin proteins and actin ... Machnicka B, Grochowalska R, Bogusławska DM, Sikorski AF, Lecomte MC (January 2012). "Spectrin-based skeleton as an actor in ...
Frappier T, Regnouf F, Pradel LA (December 1987). "Binding of brain spectrin to the 70-kDa neurofilament subunit protein". ... "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 (2): 521-527. doi:10.1042/ ...
"Entrez Gene: SYNE2 spectrin repeat containing, nuclear envelope 2". Rajgor D, Mellad JA, Autore F, Zhang Q, Shanahan CM (Jul ... Nesprins are modular proteins with a central extended spectrin-repeat (SR) rod domain and a C-terminal Klarsicht/ANC-1/Syne ... The human SYNE2 gene consists of 116 exons and encodes nesprin-2, a member of the nuclear envelope (NE) spectrin-repeat ( ... 2002). "Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple ...
May 2002). "Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain". Molecular and Cellular Biology. 22 (10 ...
... it is generally true that α-spectrin mutations result in an inability of α-spectrin to interact properly with β-spectrin to ... These αβ heterodimers then combine to form spectrin tetramers. These spectrin tetramers are among the basic structural subunits ... Less common than spectrin mutations are band 4.1 mutations. Spectrin tetramers must bind to actin in order to create a proper ... are in genes for the polypeptides α-spectrin or β-spectrin. These two polypeptides combine with one another in vivo to form an ...
"Interaction domains of neurofilament light chain and brain spectrin". Biochem. J. 275 (Pt 2): 521-7. doi:10.1042/bj2750521. PMC ... are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin". J. ...
Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha ... Alpha II-spectrin most commonly exists in a heterodimer with alpha II and beta II spectrin subunits; and dimers typically self- ... As opposed to alpha I-spectrin that is principally found in erythrocytes, alpha II-spectrin is expressed in most tissues. In ... Fourthly, a six amino acid insert in the twenty-first spectrin motif with unknown function has been reported. Alpha II-spectrin ...
The Alpha-1 refers the Alpha-1 Subunit of the Spectrin protein. The Beta refers the Beta Subunit of the Spectrin protein. These ... The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of ... Decreased surface area may be produced by two different mechanisms: Defects of Spectrin, Ankyrin (most commonly), or Protein ... Spectrin (alpha and beta) Ankyrin Band-3 Protein Protein-4.2 Lesser proteins of significance Hereditary spherocytosis can be an ...
Holleran EA, Ligon LA, Tokito M, Stankewich MC, Morrow JS, Holzbaur EL (September 2001). "beta III spectrin binds to the Arp1 ... Holleran EA, Tokito MK, Karki S, Holzbaur EL (December 1996). "Centractin (ARP1) associates with spectrin revealing a potential ... a role for spectrin and acidic phospholipids". Molecular Cell. 7 (1): 173-83. doi:10.1016/S1097-2765(01)00165-4. PMID 11172722 ... through its association with β-spectrin. The pointed end complex (PEC) has been shown to be involved in selective cargo binding ...
Similarly, spectrin plays a role in Drosophila neurons. Knock-out of α or β spectrin in D. melanogaster results in neurons that ... In animals, spectrin forms the meshwork that provides red blood cells their shape. The spectrin gene family has undergone ... Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms ... Spectrin subunits may also be cleaved by caspase family enzymes, and calpain and caspase produce different spectrin breakdown ...
The terminal web of the intestinal brush border contains a spectrin-like protein, TW 260/240 (Glenney, J. R., Jr., P. Glenney, ... The terminal web of the intestinal brush border contains a spectrin-like protein, TW 260/240 (Glenney, J. R., Jr., P. Glenney, ... M Pearl, D Fishkind, M Mooseker, D Keene, T Keller; Studies on the spectrin-like protein from the intestinal brush border, TW ... The spectrin-related molecule, TW-260/240, cross-links the actin bundles of the microvillus rootlets in the brush borders of ...
SOLUTION STRUCTURE OF THE SPECTRIN REPEAT, NMR, 20 STRUCTURES ... ALPHA SPECTRIN: A. SMTL:PDB. SMTL Chain Id:. PDB Chain Id:. A. ... SOLUTION STRUCTURE OF THE SPECTRIN REPEAT, NMR, 20 STRUCTURES Coordinates. PDB Format Method. SOLUTION NMR Oligo State. monomer ... Pascual, J. et al., Solution structure of the spectrin repeat: a left-handed antiparallel triple-helical coiled-coil. J.Mol. ...
We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells ... These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, ... Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset ... Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and ...
SPEC; Spectrin repeats. pfam01593. Location:289 → 826. Amino_oxidase; Flavin containing amine oxidoreductase. pfam04433. ...
Spectrin deficiency. Spectrin deficiency is the most common defect in HS. The biochemical nature and the degree of spectrin ... Heterozygotes for alpha-spectrin defects produce sufficient normal alpha-spectrin to balance normal beta-spectrin production. ... This leads to a defective binding of spectrin to protein 4.1. Mutations involving the alpha-spectrin beta-spectrin gene also ... Defects of beta-spectrin are more likely to be expressed in the heterozygous state because synthesis of beta-spectrin is the ...
SYNE1: spectrin repeat containing nuclear envelope protein 1. *SYNGAP1: synaptic Ras GTPase activating protein 1 ...
spectrin, beta, non-erythrocytic 4. located_in. IDA. ISO. MMO:0000538. PMID:28426968. PMID:11086001. (MGI:2181223,PMID:11807096 ...
Categories: Spectrin Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, CopyrightRestricted 1 images ...
Crystal Structure of Repeats 14-16 of Beta2-Spectrin. 3f31. Crystal Structure of the N-terminal region of AlphaII-spectrin ... Crystal Structure of first N-terminal utrophin spectrin repeat. 3uum. Crystal Structure of N-terminal first spectrin repeat of ... Crystal Structure of the Erythrocyte Spectrin Tetramerization Domain Complex. 3pdy. Structure of the third and fourth spectrin ... Spectrin repeats [ (PUBMED:8266097) ] are found in several proteins involved in cytoskeletal structure. These include spectrin ...
Fold a.7: Spectrin repeat-like [46965] (16 superfamilies). 3 helices; bundle, closed, left-handed twist; up-and-down. ...
... not spectrin, as a major component. The platelet membrane skeleton regulates the same cellular functions as the red blood cell ...
Spectrin deficient inherited hemolytic anemias in the mouse: Characterization by spectrin synthesis and mRNA activity in ...
βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in ...
Mazda CX-5 GT 150 BHP Stunning Car Huge Spec Trin. Price. €. 31,450 ...
... and spectrin [87]. In addition, EspC confers enhanced lysozyme resistance to EPEC [87] and serves as a substratum for adherence ...
... hydrophobic residue reduces the thermodynamic stability of a spectrin repeating unit. Pantazatos DP, MacDonald RI. Pantazatos ...
Raphael Y, Athey BD, Wang Y, Lee MK, Altshculer RA: F-actin, tubulin, and spectrin in the organ of Corti: comparative ...
Through recruiting βHeavy-Spectrin and MyosinV to the apical membrane, Crumbs maintains the Rab6-, Rab11- and Rab30-dependent ...
As such, the roles of actin crosslinking proteins were less well explored, but members of the spectrin repeat family were ...
The latter are tethered to Ankyrin G and β-spectrin, and linked to the cytoskeleton by syntrophins. [20, 21] At the endplate, ...
Microtubule minus-end-targeting proteins (−TIPs) of the calmodulin-regulated spectrin-associated protein (CAMSAP) and Patronin ... By contrast, information on microtubule minus-end-targeting proteins (−TIPs), such as the calmodulin-regulated spectrin- ...
spectrin alpha, erythrocytic 1 [S.... ST8SIA4. 7903. ST8SIA4. ST8 alpha-N-acetyl-neuraminide al.... ...
Spectrin™ for Cats Regular price $19.95 Regular price $19.95 Sale price $19.95 ...
Spectrin deficiency. Spectrin deficiency is the most common defect in HS. The biochemical nature and the degree of spectrin ... Heterozygotes for alpha-spectrin defects produce sufficient normal alpha-spectrin to balance normal beta-spectrin production. ... This leads to a defective binding of spectrin to protein 4.1. Mutations involving the alpha-spectrin beta-spectrin gene also ... Defects of beta-spectrin are more likely to be expressed in the heterozygous state because synthesis of beta-spectrin is the ...
Rattus norvegicus similar to calmodulin regulated spectrin-associated protein 1 (LOC296580), mRNA." ...
  • Approximately 50% of patients with severe recessive HS have a point mutation at codon (969) that results in an amino acid substitution (alanine [Ala]/aspartic acid [Asp]) at the corresponding site in the alpha-spectrin protein. (medscape.com)
  • Thus, this abnormal mRNA disappears before it can make any alpha-spectrin protein at all. (scitechdaily.com)
  • The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer. (wikipedia.org)
  • Spectrin subunits may also be cleaved by caspase family enzymes, and calpain and caspase produce different spectrin breakdown products which can be detected by western blotting with appropriate antibodies. (wikipedia.org)
  • In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome. (ox.ac.uk)
  • These include spectrin alpha and beta subunits [ ( PUBMED:12672815 ) ( PUBMED:15062087 ) ], alpha-actinin [ ( PUBMED:10481917 ) ] and dystrophin. (embl.de)
  • To understand the molecular basis for spectrin's mechanical properties, one must determine how spectrin subunits interact with each other. (embl.de)
  • The alpha- and beta-subunits of spectrin are made of repeated homologous units of 106 residues. (embl.de)
  • The newly described crystallographic structures of two consecutive homologous repeats of human alpha-actinin, a member of the spectrin superfamily, shed new light on alpha-actinin interchain binding properties. (embl.de)
  • In humans, association with the intracellular face of the plasma membrane is by indirect interaction, through direct interactions with protein 4.1 and ankyrin, with the transmembrane ion transporter band 3 Protein 4.2 binds the spectrin tail region to the transmembrane protein glycophorin A. In animals, spectrin forms the meshwork that provides red blood cells their shape. (wikipedia.org)
  • This leads to a defective binding of spectrin to protein 4.1. (medscape.com)
  • Quantitative and functional abnormalities of certain RBC membrane proteins (alpha- and beta-spectrin, protein 4.1, F-actin, ankyrin) cause hemolytic anemias. (msdmanuals.com)
  • The erythrocyte model demonstrates the importance of the spectrin cytoskeleton in that mutations in spectrin commonly cause hereditary defects of the erythrocyte, including hereditary elliptocytosis and rarely hereditary spherocytosis. (wikipedia.org)
  • Mutations in βH spectrin in C. elegans cause defects in morphogenesis resulting in a significantly shorter, but otherwise mostly normal, animal that moves and reproduces. (wikipedia.org)
  • Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development. (ox.ac.uk)
  • Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. (ox.ac.uk)
  • Mutations of alpha-spectrin are associated with recessive forms of HS, whereas mutations of beta-spectrin occur in autosomal dominant forms of HS. (medscape.com)
  • His team started by looking for mutations in the exons of the patients' alpha-spectrin genes. (scitechdaily.com)
  • We even had a couple of patients with no exon mutations in their alpha-spectrin genes, even though they had rHS with alpha-spectrin-deficient red blood cells. (scitechdaily.com)
  • Mutations involving the alpha-spectrin beta-spectrin gene also occur, each resulting in spectrin deficiency. (medscape.com)
  • Several other beta-spectrin mutations have been identified. (medscape.com)
  • Some of these mutations result in impaired beta-spectrin synthesis. (medscape.com)
  • It was previously shown that the beta-spectrin ankyrin-binding domain binds lipid domains rich in PE in an ankyrin-dependent manner, and that its N-terminal sequence is crucial in interactions with phospholipids. (biomedcentral.com)
  • In this study, the effect of the full-length ankyrin-binding domain of β-spectrin on natural erythrocyte and HeLa cell membranes was tested. (biomedcentral.com)
  • It was found that, when encapsulated in resealed erythrocyte ghosts, the protein representing the full-length ankyrin-binding domain strongly affected the shape and barrier properties of the erythrocyte membrane, and induced partial spectrin release from the membrane, while truncated mutants had no effect. (biomedcentral.com)
  • Int. 31 (2007) 1482-94), overexpression of the full-length GFP-tagged ankyrin-binding domain aggregated and induced aggregation of endogenous spectrin, but this was not the case with overexpression of proteins truncated at their N-terminus. (biomedcentral.com)
  • Here, we show that the aggregation of spectrin was accompanied by the aggregation of integral membrane proteins that are known to be connected to spectrin via ankyrin, i.e. (biomedcentral.com)
  • The obtained results indicate a substantial role of the lipid-binding part of the β-spectrin ankyrin-binding domain in the determination of the membrane and spectrin-based skeleton functional properties. (biomedcentral.com)
  • Bennett, V. and Baines, A.J. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. (biomedcentral.com)
  • In animals, spectrin forms the meshwork that provides red blood cells their shape. (wikipedia.org)
  • This supports the idea that adducin mediates cytoskeletal changes associated with synaptic activity, potentially by destabilizing the actin-spectrin meshwork after strong stimulation. (jneurosci.org)
  • In the light microscope the basic shape of the red blood cell could still be seen as the spectrin-containing submembranous cytoskeleton preserved the shape of the cell in outline. (wikipedia.org)
  • In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain, destroying the cytoskeleton. (wikipedia.org)
  • The convenience of using erythrocytes compared to other cell types means they have become the standard model for the investigation of the spectrin cytoskeleton. (wikipedia.org)
  • In humans, a mutation within the AnkB gene results in the long QT syndrome and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue. (wikipedia.org)
  • Studies on the spectrin-like protein from the intestinal brush border, TW 260/240, and characterization of its interaction with the cytoskeleton and actin. (rupress.org)
  • There, SUB1 activates a PV-resident cysteine protease called SERA6, enabling host RBC rupture through SERA6-mediated degradation of the RBC cytoskeleton protein β-spectrin. (crick.ac.uk)
  • Spectrin cleavage causes the membrane to form blebs and ultimately to be degraded, usually leading to the death of the cell. (wikipedia.org)
  • Genetic ablation of MSA180 mimics SERA6 disruption, producing a fatal block in β-spectrin cleavage and RBC rupture. (crick.ac.uk)
  • Drug-like inhibitors of SERA6 autoprocessing similarly prevent β-spectrin cleavage and egress in both P. falciparum and the emerging zoonotic pathogen P. knowlesi. (crick.ac.uk)
  • Spectrin, the major component of the membrane skeleton that provides elasticity to the cell, contains tandemly repeated sequences of 106 amino acid residues. (embl.de)
  • Spectrin, the major component of the erythroid membrane skeleton, is a long, asymmetrical rodlike protein that interacts with several other proteins to form a two-dimensional membrane skeleton. (embl.de)
  • The spectrin-based membrane skeleton is asymmetric and remodels during neural development in C. elegans . (bvsalud.org)
  • and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). (ox.ac.uk)
  • Red cell membranes isolated from individuals with autosomal recessive HS have only 40-50% of the normal amount of spectrin (relative to band protein 3). (medscape.com)
  • A novel mutation in the gene that encodes alpha-spectrin, a protein essential for normal red blood cell membranes, is responsible for many cases of recessive hereditary spherocytosis (rHS), the most severe form of the disease, reports Gallagher's team in a paper published in the Journal of Clinical Investigation (JCI). (scitechdaily.com)
  • Similarly, spectrin plays a role in Drosophila neurons. (wikipedia.org)
  • Knock-out of α or β spectrin in D. melanogaster results in neurons that are morphologically normal but have reduced neurotransmission at the neuromuscular junction. (wikipedia.org)
  • We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. (ox.ac.uk)
  • Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. (wikipedia.org)
  • Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure. (wikipedia.org)
  • Spectrin repeats [ ( PUBMED:8266097 ) ] are found in several proteins involved in cytoskeletal structure. (embl.de)
  • Both spectrin and alpha-actinin are components of the cytoskeletal network, the integrity of which is based on multiple and complex interactions. (embl.de)
  • Spectrin deficiency can result from impaired synthesis of spectrin or from quantitative or qualitative deficiencies of other proteins that integrate spectrin into the red cell membrane. (medscape.com)
  • In the absence of those binding proteins, free spectrin is degraded, leading to spectrin deficiency. (medscape.com)
  • Sequence alignments and phylogenetic trees of these domains allow us to interpret the evolutionary relationship between these proteins, concluding that spectrin evolved from alpha-actinin by an elongation process that included two duplications of a block of seven repeats. (embl.de)
  • The present status of erythrocyte spectrin structure: the 106-residue repetitive structure is a basic feature of an entire class of proteins. (embl.de)
  • The spectrin gene family has undergone expansion during evolution. (wikipedia.org)
  • But the team had been looking in the wrong place, Gallagher said: The mutation they identified was hidden in the intron of the alpha-spectrin gene. (scitechdaily.com)
  • So, we did whole genome sequencing," he continued, "and found a rare variant in an alpha-spectrin gene intron, which had been described only once in the literature. (scitechdaily.com)
  • Bennett, V. and Branton, D. Selective association of spectrin with the cytoplasmic surface of Human erythrocyte plasma membranes. (biomedcentral.com)
  • Bennett, V. and Stenbuck, P.J. The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes. (biomedcentral.com)
  • Alpha-spectrin provides both strength and flexibility to red blood cell membranes, helping cells maintain their shape and integrity while making their circuit through the body, he explained. (scitechdaily.com)
  • Cells without sufficient alpha-spectrin in their membranes suffer membrane damage, losing strength and flexibility. (scitechdaily.com)
  • It was already known rHS was linked to recessively inherited abnormalities in alpha-spectrin. (scitechdaily.com)
  • Yu, J. and Goodman, S.R. Syndeins: the spectrin-binding protein(s) of the human erythrocyte membrane. (biomedcentral.com)
  • Heterozygotes for alpha-spectrin defects produce sufficient normal alpha-spectrin to balance normal beta-spectrin production. (medscape.com)
  • Defects of beta-spectrin are more likely to be expressed in the heterozygous state because synthesis of beta-spectrin is the rate-limiting factor. (medscape.com)
  • A mutation in β spectrin in C. elegans results in an uncoordinated phenotype in which the worms are paralysed and much shorter than wild-type. (wikipedia.org)
  • It found that the intron mutation strengthened an alternate "branch point" in splicing, which resulted in abnormal mRNA, or incorrect instructions for alpha-spectrin assembly. (scitechdaily.com)
  • Written by Sophia LeungEdited by Dr Hannah K Shorrock In SCA5, the N-terminus of β‑spectrin induces toxicity and therefore a new target for therapeutics to treat SCA5. (ataxia.org)
  • The research group led by Dr. Adam Avery explored the roles a fragment of the β‑spectrin protein, the N-terminus, plays in SCA5. (ataxia.org)
  • Here I present evidence that interchain binding at the tail end of the spectrin molecule is likely to occur via a mechanism similar to that observed for alpha-actinin. (embl.de)
  • Alpha-actinin and spectrin structures: an unfolding family story. (embl.de)
  • In myocardial cells, aII spectrin distribution is coincident with Z-discs and the plasma membrane of myofibrils. (wikipedia.org)
  • Goodman, S.R., Zagon, I.S. and Kulikowski, R.R. Identification of a spectrin-like protein in nonerythroid cells. (biomedcentral.com)
  • In red blood cells, the integrity of the spectrin network is essential for normal cell shape and elasticity. (embl.de)
  • These damaged, alpha-spectrin-deficient red blood cells are then trapped and destroyed by the spleen. (scitechdaily.com)
  • This underproduction of alpha-spectrin results in an increased proportion of alpha-spectrin-deficient red blood cells, which then presents in patients as severe hemolytic anemia. (scitechdaily.com)
  • Alpha-actinin and spectrin have common structural domains. (embl.de)
  • We suggest that the shared domain structure indicates common structural principles or interactions of spectrin and alpha-actinin and reflects their common evolution. (embl.de)
  • Morphological studies on purified TW 260/240 using the rotary shadowing technique confirm earlier results that this protein is spectrin-like and is in the tetrameric state in buffers of low ionic strength. (rupress.org)
  • The biochemical nature and the degree of spectrin deficiency are reported to correlate with the extent of spherocytosis, the degree of abnormality on osmotic fragility test results, and the severity of hemolysis. (medscape.com)
  • Solution structure of the spectrin repeat: a left-handed antiparallel triple-helical coiled-coil. (expasy.org)
  • The spectrin repeat forms a three-helix bundle. (embl.de)
  • Evolution of the spectrin repeat. (embl.de)
  • In the recently reported partial sequence of the chicken non-muscle alpha-actinin, a repetitive sequence homologous to the internal repeat in spectrin occurs several times. (embl.de)
  • This became known as a red blood cell "ghost" (spectre), and so the major protein of the ghost was named spectrin. (wikipedia.org)
  • In the autosomal dominant form of HS, red cell spectrin levels range from 60-80% of normal. (medscape.com)
  • The spectrin protein is a tetramer made up of alpha-beta dimers. (medscape.com)
  • β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. (ox.ac.uk)
  • Synthesis of alpha-spectrin is threefold greater than that of beta-spectrin. (medscape.com)
  • Bialkowska, K., Saido, T.C. and Fox, J.E.B. SH3 domain of spectrin participates in the activation of Rac in specialized calpain-induced integrin signaling complexes. (biomedcentral.com)
  • Dimeric spectrin is formed by the lateral association of αI and βI monomers to form a dimer. (wikipedia.org)
  • Spectrin deficiency is the most common defect in HS. (medscape.com)

No images available that match "spectrin"