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Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex
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 indiv...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148225/ https://www.ncbi.nlm.nih.gov/pubmed/10189375 |
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author | Crosbie, Rachelle H. Lebakken, Connie S. Holt, Kathleen H. Venzke, David P. Straub, Volker Lee, Jane C. Grady, R. Mark Chamberlain, Jeffery S. Sanes, Joshua R. Campbell, Kevin P. |
author_facet | Crosbie, Rachelle H. Lebakken, Connie S. Holt, Kathleen H. Venzke, David P. Straub, Volker Lee, Jane C. Grady, R. Mark Chamberlain, Jeffery S. Sanes, Joshua R. Campbell, Kevin P. |
author_sort | Crosbie, Rachelle H. |
collection | PubMed |
description | 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 α-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG–SPN subcomplex. |
format | Text |
id | pubmed-2148225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21482252008-05-01 Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex Crosbie, Rachelle H. Lebakken, Connie S. Holt, Kathleen H. Venzke, David P. Straub, Volker Lee, Jane C. Grady, R. Mark Chamberlain, Jeffery S. Sanes, Joshua R. Campbell, Kevin P. J Cell Biol Regular Articles 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 α-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG–SPN subcomplex. The Rockefeller University Press 1999-04-05 /pmc/articles/PMC2148225/ /pubmed/10189375 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Regular Articles Crosbie, Rachelle H. Lebakken, Connie S. Holt, Kathleen H. Venzke, David P. Straub, Volker Lee, Jane C. Grady, R. Mark Chamberlain, Jeffery S. Sanes, Joshua R. Campbell, Kevin P. Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title | Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title_full | Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title_fullStr | Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title_full_unstemmed | Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title_short | Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex |
title_sort | membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148225/ https://www.ncbi.nlm.nih.gov/pubmed/10189375 |
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