Dystrophin-associated proteins that play role in the formation of a transmembrane link between laminin-2 and DYSTROPHIN. Both the alpha and the beta subtypes of dystroglycan originate via POST-TRANSLATIONAL PROTEIN PROCESSING of a single precursor protein.
An autosomally-encoded 376-kDa cytoskeletal protein that is similar in structure and function to DYSTROPHIN. It is a ubiquitously-expressed protein that plays a role in anchoring the CYTOSKELETON to the PLASMA MEMBRANE.

Binding of the G domains of laminin alpha1 and alpha2 chains and perlecan to heparin, sulfatides, alpha-dystroglycan and several extracellular matrix proteins. (1/520)

The C-terminal G domain of the mouse laminin alpha2 chain consists of five lamin-type G domain (LG) modules (alpha2LG1 to alpha2LG5) and was obtained as several recombinant fragments, corresponding to either individual modules or the tandem arrays alpha2LG1-3 and alpha2LG4-5. These fragments were compared with similar modules from the laminin alpha1 chain and from the C-terminal region of perlecan (PGV) in several binding studies. Major heparin-binding sites were located on the two tandem fragments and the individual alpha2LG1, alpha2LG3 and alpha2LG5 modules. The binding epitope on alpha2LG5 could be localized to a cluster of lysines by site-directed mutagenesis. In the alpha1 chain, however, strong heparin binding was found on alpha1LG4 and not on alpha1LG5. Binding to sulfatides correlated to heparin binding in most but not all cases. Fragments alpha2LG1-3 and alpha2LG4-5 also bound to fibulin-1, fibulin-2 and nidogen-2 with Kd = 13-150 nM. Both tandem fragments, but not the individual modules, bound strongly to alpha-dystroglycan and this interaction was abolished by EDTA but not by high concentrations of heparin and NaCl. The binding of perlecan fragment PGV to alpha-dystroglycan was even stronger and was also not sensitive to heparin. This demonstrated similar binding repertoires for the LG modules of three basement membrane proteins involved in cell-matrix interactions and supramolecular assembly.  (+info)

Characterization of the transmembrane molecular architecture of the dystroglycan complex in schwann cells. (2/520)

We have demonstrated previously 1) that the dystroglycan complex, but not the sarcoglycan complex, is expressed in peripheral nerve, and 2) that alpha-dystroglycan is an extracellular laminin-2-binding protein anchored to beta-dystroglycan in the Schwann cell membrane. In the present study, we investigated the transmembrane molecular architecture of the dystroglycan complex in Schwann cells. The cytoplasmic domain of beta-dystroglycan was co-localized with Dp116, the Schwann cell-specific isoform of dystrophin, in the abaxonal Schwann cell cytoplasm adjacent to the outer membrane. beta-dystroglycan bound to Dp116 mainly via the 15 C-terminal amino acids of its cytoplasmic domain, but these amino acids were not solely responsible for the interaction of these two proteins. Interestingly, the beta-dystroglycan-precipitating antibody precipitated only a small fraction of alpha-dystroglycan and did not precipitate laminin and Dp116 from the peripheral nerve extracts. Our results indicate 1) that Dp116 is a component of the submembranous cytoskeletal system that anchors the dystroglycan complex in Schwann cells, and 2) that the dystroglycan complex in Schwann cells is fragile compared with that in striated muscle cells. We propose that this fragility may be attributable to the absence of the sarcoglycan complex in Schwann cells.  (+info)

Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex. (3/520)

The dystrophin-glycoprotein complex (DGC) is a multisubunit complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. The proteins of the DGC are structurally organized into distinct subcomplexes, and genetic mutations in many individual components are manifested as muscular dystrophy. We recently identified a unique tetraspan-like dystrophin-associated protein, which we have named sarcospan (SPN) for its multiple sarcolemma spanning domains (Crosbie, R.H., J. Heighway, D.P. Venzke, J.C. Lee, and K.P. Campbell. 1997. J. Biol. Chem. 272:31221-31224). To probe molecular associations of SPN within the DGC, we investigated SPN expression in normal muscle as a baseline for comparison to SPN's expression in animal models of muscular dystrophy. We show that, in addition to its sarcolemma localization, SPN is enriched at the myotendinous junction (MTJ) and neuromuscular junction (NMJ), where it is a component of both the dystrophin- and utrophin-glycoprotein complexes. We demonstrate that SPN is preferentially associated with the sarcoglycan (SG) subcomplex, and this interaction is critical for stable localization of SPN to the sarcolemma, NMJ, and MTJ. Our experiments indicate that assembly of the SG subcomplex is a prerequisite for targeting SPN to the sarcolemma. In addition, the SG- SPN subcomplex functions to stabilize alpha-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG-SPN subcomplex.  (+info)

Further evidence for the organisation of the four sarcoglycans proteins within the dystrophin-glycoprotein complex. (4/520)

Based on the pattern of distribution of the SG proteins in patients with LGMD2C and 2D, and on the observed decreased abundance of dystrophin through WB in some sarcoglycans (SG) patients, we have recently suggested that alpha, beta and delta subunits of sarcoglycan complex might be more closely associated and that gamma-SG might interact more directly with dystrophin. Two additional SG patients here reported give further support to these suggestions: an LGMD2F patient showed patchy labelling for gamma-SG, despite the lack of staining of the other three SG proteins; an LGMD2C boy showed deficiency in dystrophin by means of WB and IF, comparable with an DMD manifesting carrier. These two patients represent further evidence of a closer relation of alpha, beta and delta-SG than of gamma-SG and of the possible association of gamma-SG with dystrophin. In addition the LGMD2C patient illustrates the potential risk of misdiagnosis using only dystrophin analysis, in cases with no positive family history, or when DNA analysis is not informative.  (+info)

Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by dystroglycan. (5/520)

Expression of dystroglycan (DG) by cultured bovine aortic endothelial (BAE) cells was confirmed by cDNA cloning from a BAE cDNA library, Northern blotting of mRNA, Western blotting of membrane proteins, and double immunostaining with antibodies against betaDG and platelet endothelial cell adhesion molecule-1. Immunocytochemical analysis revealed localization of DG in multiple plaques on the basal side of resting cells. This patchy distribution was obscured in migrating cells, in which the most prominent staining was observed in the trailing edge anchoring the cells to the substratum. Biotin-labeled laminin-1 overlay assay of dissociated BAE membrane proteins indicated the interaction of laminin-1 with alphaDG. The laminin alpha5 globular domain fragment expressed in bacteria and labeled with biotin could also bind alphaDG on the membrane blot, and the unlabeled fragment disrupted the binding of biotin-laminin-1 to alphaDG. The interaction of biotin-laminin-1 with alphaDG was inhibited by soluble alphaDG contained in the conditioned medium from DG cDNA-transfected BAE cells and by a series of glycosaminoglycans (heparin, dextran sulfate, and fucoidan). Soluble alphaDG in the conditioned medium inhibited the adhesion of BAE cells to laminin-1-coated dishes, whereas it had no effect on their adhesion to fibronectin. All three glycosaminoglycans that disrupted the biotin-laminin-1 binding to alphaDG inhibited BAE cell adhesion to laminin-1, whereas they failed to inhibit the adhesion to fibronectin. These results indicate a role of DG as a non-integrin laminin receptor involved in vascular endothelial cell adhesion to the extracellular matrix.  (+info)

Basement membranes: Putting up the barriers. (6/520)

The basement membrane is a highly organized extracellular matrix with adhesive and barrier functions. Assembly of this matrix uses two types of cell surface receptor, integrins and dystroglycan, to coordinate formation of a polygonal network of laminin, a major basement membrane protein.  (+info)

Multiplex Western blotting system for the analysis of muscular dystrophy proteins. (7/520)

A multiplex system of Western blotting is presented in which most of the current muscular dystrophy proteins can be analyzed simultaneously on one pair of blots. This represents a significant improvement in efficiency and cost for this type of analysis. The final diagnosis is more quickly achieved in patients where several possible diagnoses are indicated after clinical appraisal, and those with unusual presentations may be quickly resolved. The method uses a biphasic polyacrylamide gel system, which enables the corresponding blot to be probed simultaneously with a cocktail of monoclonal antibodies. The gel is optimized so that large proteins of more than 200 kd (eg, dystrophin, dysferlin, and myosin heavy chain) can be analyzed in the top part, while smaller proteins under 150 kd (eg, calpain 3, the 80-kd fragment of laminin alpha2 chain, all of the sarcoglycans, and caveolin 3) are separated in the lower phase. This basic system could be used for different combinations of antibodies as new muscular dystrophy proteins are identified and require examination. In addition, analysis of the laminin alpha2 chain of merosin showed that this protein was expressed as a doublet or triplet set of bands in many patients with active muscle pathology. This may indicate the existence of an embryonic isoform, which is re-expressed in regenerating fibers.  (+info)

Acetylcholinesterase clustering at the neuromuscular junction involves perlecan and dystroglycan. (8/520)

Formation of the synaptic basal lamina at vertebrate neuromuscular junction involves the accumulation of numerous specialized extracellular matrix molecules including a specific form of acetylcholinesterase (AChE), the collagenic-tailed form. The mechanisms responsible for its localization at sites of nerve- muscle contact are not well understood. To understand synaptic AChE localization, we synthesized a fluorescent conjugate of fasciculin 2, a snake alpha-neurotoxin that tightly binds to the catalytic subunit. Prelabeling AChE on the surface of Xenopus muscle cells revealed that preexisting AChE molecules could be recruited to form clusters that colocalize with acetylcholine receptors at sites of nerve-muscle contact. Likewise, purified avian AChE with collagen-like tail, when transplanted to Xenopus muscle cells before the addition of nerves, also accumulated at sites of nerve-muscle contact. Using exogenous avian AChE as a marker, we show that the collagenic-tailed form of the enzyme binds to the heparan-sulfate proteoglycan perlecan, which in turn binds to the dystroglycan complex through alpha-dystroglycan. Therefore, the dystroglycan-perlecan complex serves as a cell surface acceptor for AChE, enabling it to be clustered at the synapse by lateral migration within the plane of the membrane. A similar mechanism may underlie the initial formation of all specialized basal lamina interposed between other cell types.  (+info)

Dystroglycans are a type of protein that play a crucial role in the structure and function of the muscle membrane (sarcolemma). They are an essential component of the dystrophin-glycoprotein complex, which helps maintain the stability and integrity of the sarcolemma during muscle contraction and relaxation.

Dystroglycans consist of two subunits: alpha-dystroglycan and beta-dystroglycan. Alpha-dystroglycan is a large, heavily glycosylated protein that extends from the intracellular space to the extracellular matrix, where it interacts with various extracellular matrix proteins such as laminin and agrin. Beta-dystroglycan, on the other hand, spans the muscle membrane and binds to dystrophin, a cytoskeletal protein that helps maintain the structural integrity of the sarcolemma.

Mutations in genes encoding for proteins involved in the glycosylation of alpha-dystroglycan can lead to a group of genetic disorders known as congenital muscular dystrophies, which are characterized by muscle weakness, hypotonia, and developmental delays. These disorders include Walker-Warburg syndrome, Fukuyama congenital muscular dystrophy, and Muscle-Eye-Brain disease, among others.

Utrophin is a protein that is found in muscle cells. It is similar in structure and function to dystrophin, which is a protein that is deficient or abnormal in people with Duchenne and Becker muscular dystrophy. Utrophin is present in both fetal and adult muscle, but its expression is usually limited to the nerve endings of the muscle fibers. However, in certain conditions such as muscle injury or disease, utrophin can be upregulated and expressed more widely throughout the muscle fiber. Research has shown that increasing the levels of utrophin in muscle cells could potentially compensate for the lack of dystrophin and provide a therapeutic approach to treating muscular dystrophy.

... dystroglycans (MIM 128239); and sarcoglycans, such as adhalin, a 50-kD transmembrane protein (Roberds et al., 1993).[supplied ...
The lamina lucida layer is made up of laminin, integrins, entactins, and dystroglycans. Integrins are a key component of ... nidogens dystroglycans Lamina densa collagen IV (coated with perlecan, rich in heparan sulfate) Attaching proteins (between the ...
Dystroglycans at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Overview at sdbonline.org (Articles with ... Côté PD, Moukhles H, Lindenbaum M, Carbonetto S (November 1999). "Chimaeric mice deficient in dystroglycans develop muscular ...
... and beta-dystroglycans (see MIM 128239), and the sarcoglycans (see, e.g., SGCA; MIM 600119) (Crosbie et al., 2000).[supplied by ...
... interacts with dystroglycans, which are transmembrane proteins that connect the DGC to the extracellular matrix. This ... Sarcoglycans bind to SSPN and form the SG-SSPN complex, which interacts with dystroglycans (DG) and Utrophin leading to the ... and dystroglycans. One of the key functions of sarcospan is to help stabilize the DGC and promote its proper localization at ...
This complex stabilizes the association of dystrophin with the dystroglycans and contributes to the stability of the plasma ...
... including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and ...
... including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its ...
... dystroglycans MeSH D12.776.210.500.410.750 - sarcoglycans MeSH D12.776.210.500.570.590 - myod protein MeSH D12.776.210.500. ...
... contains various integral and peripheral membrane proteins such as dystroglycans and sarcoglycans, which are thought to be ...
... dystroglycans (MIM 128239); and sarcoglycans, such as adhalin, a 50-kD transmembrane protein (Roberds et al., 1993).[supplied ...
The lamina lucida layer is made up of laminin, integrins, entactins, and dystroglycans. Integrins are a key component of ... nidogens dystroglycans Lamina densa collagen IV (coated with perlecan, rich in heparan sulfate) Attaching proteins (between the ...
It contains several proteins known as sarcoglycans and others known as dystroglycans. Mutations of each of these proteins, as ... dystroglycans, dysferlin, and others, are recognized. Abnormalities of proteins of the nucleus, cytoskeletal proteins and the ...
At the sarcolemma of skeletal muscle, there is a complex composed of several proteins, including dystroglycans, sarcoglycans, ...
... and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of .... cl00085. Location:584 → 658. FReD; ...
... a heteromeric complex related to the dystroglycans. Neuron 12, 1173-1180 (1994) ...
... referred to as sarcoglycans and dystroglycans. [3, 4] ...
Koshimizu, H., Matsuoka, H., Nakajima, Y., Kawai, A., Ono, J., Ohta, K. I., Miki, T., Sunagawa, M., Adachi, N. & Suzuki, S., 12-2021, In: Neuropsychopharmacology reports. 41, 4, p. 485-495 11 p.. Research output: Contribution to journal › Article › peer-review ...
Dystroglycans MeSH DeCS ID:. 38684 Unique ID:. D049028 Documents indexed in the Virtual Health Library (VHL):. Click here to ...
on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology & American College of Cardiology, Dec 1 2015, In: Circulation. 132, 22, p. e281-e291. Research output: Contribution to journal › Article › peer-review ...
Dive into the research topics where Joshua Akey is active. These topic labels come from the works of this person. Together they form a unique fingerprint ...
Dystroglycans Medicine & Life Sciences 92% * Muscular Dystrophies Medicine & Life Sciences 75% * Ligands Medicine & Life ...
Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis. J ... Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis. J ... Regele H.M., Fillipovic E., Langer B., et al: Glomerular expression of dystroglycans is reduced in minimal change nephrosis but ...
abstract::Alpha-/beta-dystroglycans (DG) located at the outmost layer of myelin sheath play a critical role in its formation ...
... transmembrane sarcoglycans and dystroglycans, and extracellular basal lamina with laminin 2. 362. Cognitive impairments are ...
LGMD2I belongs to a family of disorders with abnormal alpha dystroglycans labelling on muscle biopsy, caused by mutations in ...
... the sarcoglycans and the dystroglycans. As little as 10 mg of tissue is sufficient for the analysis of all diagnostically ...
Animals, Blotting, Western, Carrier Proteins, Desmin, Dystroglycans, Dystrophin-Associated Proteins, Fetus, Humans, ...
... including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and ...
... including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanos Fator 1 Associado a Receptor de TNF TNF Receptor-Associated Factor 1 Factor 1 Asociado a Receptor ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
Dystroglycans Distroglicanas Distroglicanos Dystrophin-Associated Proteins Proteínas Associadas à Distrofina Proteínas ...
  • Cadherin-homologous domains present in metazoan dystroglycans and alpha/epsilon sarcoglycans, yeast Axl2p and in a very large protein from magnetotactic bacteria. (embl.de)
  • Shown is a segment of a myofiber plasma membrane, with the intracellular dystrophin-based membrane cytoskeleton, transmembrane sarcoglycans and dystroglycans, and extracellular basal lamina with laminin 2. (tradingsignalsforex.com)
  • This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. (nih.gov)
  • It helps maintain the structure of muscle tissue by attaching (binding) to and stabilizing the dystrophin complex, which is made up of proteins called dystrophins and dystroglycans. (medlineplus.gov)
  • The C-terminal binds with the dystrophin-associated protein complex, which consists of dystroglycans and structures that support the basal lamina, forming the dystrophin axis. (pathologycenter.jp)
  • Research at the University of Iowa, directed by Kevin Campbell, Ph.D., will explore therapeutic strategies for the treatment of various muscular dystrophies arising from the abnormal processing of muscle proteins called dystroglycans. (nih.gov)