In cell biology, an endosome is a membrane-bounded compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature. Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding to the ...
The association of the Vps35-Vps29-Vps26 complex to the cytosolic domains of cargo molecules endosomal membranes initiates the activation of retrograde trafficking and cargo capture.[16] The nucleation complex was formed through the interaction of VPS complex with GTP-activated Rab7[17] with clathrin, clathrin-adaptors and various binding proteins.[18]. The SNX-BAR dimer enters the nucleation complex via direct binding or lateral movement on endosomal surface. The increased level of Retromer SNX-BARs causes a conformational switch to a curvature-inducing mode which initiates membrane tubule formation.[19][20] Once the cargo carriers are matured, the carrier scission is then catalyzed by dynamin-II or EHD1,[21] together with the mechanical forces generated by actin polymerization and motor activity.. The cargo carrier is transported to the TGN by motor proteins such as dynein. Tethering of the cargo carrier to the recipient compartment will lead to the uncoating of the carrier which is driven by ...
... , a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene. The principal enzymatic activity of PIKfyve is to phosphorylate PtdIns3P to PtdIns(3,5)P2. PIKfyve activity is responsible for the production of both PtdIns(3,5)P2 and phosphatidylinositol 5-phosphate (PtdIns5P). PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. The reported full-length mouse and human cDNA clones encode proteins of 2052 and 2098 amino acid residues, respectively. By directly binding membrane PtdIns(3)P, the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes. Impaired PIKfyve enzymatic activity by dominant-interfering mutants, siRNA- mediated ablation or pharmacological inhibition causes endosome enlargement and cytoplasmic vacuolation due to impaired PtdIns(3,5)P2 synthesis. Thus, via PtdIns(3,5)P2 production, PIKfyve participates in several ...
The initial step of autophagosome formation of an omegasome on the endoplasmic reticulum, followed by of elongation of structures called phagophores.[3]. The formation of autophagosomes is controlled by Atg genes through Atg12-Atg5 and LC3 complexes. The conjugate of Atg12-Atg5 also interacts with Atg16 to form larger complexes. Modification of Atg5 by Atg12 is essential for the elongation of the initial membrane.[4]. After the formation of the spherical structure, the complex of ATG12-ATG5:ATG16L1 dissociates from the autophagosome. LC3 is cleaved by ATG4 protease to generate cytosolic LC3. LC3 cleavage is required for the terminal fusion of an autophagosome with its target membrane. LC3 is commonly used as a marker of autophagosomes in immunocytochemistry, because it is the essential part of the vesicle and stays associated until the last moment before its fusion. At first, autophagosomes fuse with endosomes or endosome-derived vesicles. These structures are then called amphisomes or ...
... , also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides. The protein is originally synthesised in an inactive 65 kDa proheparanase form in the golgi apparatus and transferred to late endosomes/lysosomes for transport to the cell-surface. In the lysosome it is proteolytically processed into its active form. Proteolytic processing results in the production of three products, a linker peptide an 8 kDa proheparanase fragment and a 50 kDa proheparanase fragment The 8 kDa and 50 kDa fragments form a heterodimer and it is this heterodimer that constitutes the active heparanase molecule. The linker protein is so called because prior to its excision it physically links the 8 kDa and 50 kDa proheparanase fragments. Complete excision of the linker peptide appears to be a prerequisite to the complete activation of the heparanase enzyme. Crystal structures of ...
The function of receptor-mediated endocytosis is diverse. It is widely used for the specific uptake of certain substances required by the cell (examples include LDL via the LDL receptor or iron via transferrin). The role of receptor-mediated endocytosis is well recognized up take downregulation of transmembrane signal transduction but can also promote sustained signal transduction.[3] The activated receptor becomes internalised and is transported to late endosomes and lysosomes for degradation. However, receptor-mediated endocytosis is also actively implicated in transducing signals from the cell periphery to the nucleus. This became apparent when it was found that the association and formation of specific signaling complexes is required for the effective signaling of hormones (e.g. EGF). Additionally it has been proposed that the directed transport of active signaling complexes to the nucleus might be required to enable signaling as random diffusion is too slow[4] and mechanisms permanently ...
Ras-related protein Rab-18 is a protein that in humans is encoded by the RAB18 gene. Rab18 is a ubiquitously expressed protein with particularly high expression in the brain. Rab18 was first characterised as an endosomal protein in epithelial cells of mouse kidney and intestines. Subsequent studies revealed that Rab18 has a wide intracellular distribution; localising to the Golgi complex, endoplasmic reticulum, lipid droplets, and cytosol of various cell types. In the brain, Rab18 has been isolated in association with synaptic vesicles and has been observed to localise to secretory granules in neuroendocrine cells. GRCh38: Ensembl release 89: ENSG00000099246 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000073639 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Schafer U, Seibold S, Schneider A, Neugebauer E (Feb 2000). "Isolation and characterisation of the human rab18 gene after stimulation of endothelial cells with histamine". FEBS Lett. 466 (1): 148-54. ...
Sortilin (SORT1) is a protein that in humans is encoded by the SORT1 gene on chromosome 1. This protein is a type I membrane glycoprotein in the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors. While it is ubiquitously expressed in many tissues, sortilin is most abundant in the central nervous system. At the cellular level, sortilin functions in protein transport between the Golgi apparatus, endosome, lysosome, and plasma membrane, leading to its involvement in multiple biological processes such as glucose and lipid metabolism as well as neural development and cell death. Moreover, the function and role of sortilin is now emerging in several major human diseases such as atherosclerosis and coronary artery disease, Alzheimer's disease, and cancer. The SORT1 gene also contains one of 27 loci associated with increased risk of coronary artery disease. The SORT1 gene resides on chromosome 1 at the band 1p13.3 and includes 23 exons. This gene encodes 2 isoforms through ...
Protein NDRG1 is a protein that in humans is encoded by the NDRG1 gene. This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation[citation needed]. Mutations in this gene have been reported to be causative the autosomal-recessive version of Charcot-Marie-Tooth disease known as CMT4D. It has been reported that NDRG1 localizes to the endosomes and is a Rab4a effector involved in vesicular recycling. As reviewed by Fang et al., NDRG1 is involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses, immunity, DNA repair and cell adhesion among other functions. NDRG1 is localised in the cytoplasm, nucleus and mitochondrion, at probabilities of 47.8%, 26.1% and 8.7%, respectively. In response to DNA damage NDRG1 translocates from the ...
விலங்கு உயிரணுக்களின் நுண்ணுறுப்புகளுள் ஒன்றான இலைசோசோம்கள் (lysosome) கழிவுப் பொருட்ளையும் தீங்கு விளைவிக்கும் நோய்க்கிருமிகளையும் செரிக்கும் இன்றியமையாத வேலையைச் செய்கின்றன. தாவரங்களிலும் பூஞ்சைகளிலும் இலைசோசோம்கள் இல்லை. இப்பணியை வெற்றிடப்பைகள் செய்கின்றன. இலைசோசோம் ஒரே ஒரு உறை மட்டுமே உடையது. இவ் உறைக்குள் பல வலிமையான நொதிகள் காணப்படும். இவை இந்த உறையை விட்டு வெளியே ...
The function of receptor-mediated endocytosis is diverse. It is widely used for the specific uptake of certain substances required by the cell (examples include LDL via the LDL receptor or iron via transferrin). The role of receptor-mediated endocytosis is well recognized up take downregulation of transmembrane signal transduction but can also promote sustained signal transduction.[3] The activated receptor becomes internalised and is transported to late endosomes and lysosomes for degradation. However, receptor-mediated endocytosis is also actively implicated in transducing signals from the cell periphery to the nucleus. This became apparent when it was found that the association and formation of specific signaling complexes is required for the effective signaling of hormones (e.g. EGF). Additionally it has been proposed that the directed transport of active signaling complexes to the nucleus might be required to enable signaling as random diffusion is too slow[4] and mechanisms permanently ...
... is a transport mechanism for the movement of large quantities of molecules into and out of cells. There are three main types of cytosis: endocytosis (into the cell), exocytosis (out of the cell), and transcytosis (through the cell, in and out). The word cytosis (/saɪˈtoʊsɪs/) uses combining forms of cyto- and -osis, reflecting a cellular process. The term was coined by Novikoff in 1961. Endocytosis is when a cell absorbs molecules, such as proteins, from outside the cell by engulfing it with the cell membrane. It is used by most cells, because many critical substances are large polar molecules that cannot pass through the cell membrane. The two major types of endocytosis are pinocytosis and phagocytosis. Pinocytosis Pinocytosis, also known as cell drinking, is the absorption of small aqueous particles along with the membrane receptors that recognize them. It is an example of fluid phase endocytosis and is usually a continuous process within the cell. The particles are absorbed ...
All corticosteroid hormones share cholesterol as a common precursor. Therefore, the first step in steroidogenesis is cholesterol uptake or synthesis. Cells that produce steroid hormones can acquire cholesterol through two paths. The main source is through dietary cholesterol transported via the blood as cholesterol esters within low density lipoproteins (LDL). LDL enters the cells through receptor-mediated endocytosis. The other source of cholesterol is synthesis in the cell's endoplasmic reticulum. Synthesis can compensate when LDL levels are abnormally low.[4] In the lysosome, cholesterol esters are converted to free cholesterol, which is then used for steroidogenesis or stored in the cell.[29]. The initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the cytochrome P450 family that are located in the inner membrane of mitochondria. Transport of cholesterol from the outer to the inner membrane is facilitated by steroidogenic acute regulatory protein ...