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Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex

Lookup NU author(s): Professor Volker StraubORCiD

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Abstract

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.

Publication metadata

Author(s): Straub V; Crosbie RH; Lebakken CS; Holt KH; Venzke DP; Lee JC; Grady RM; Chamberlain JS; Sanes JR; Campbell KP

Publication type: Article

Publication status: Published

Journal: Journal of Cell Biology

Year: 1999

Volume: 145

Issue: 1

Pages: 153-165

Print publication date: 05/04/1999

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1083/jcb.145.1.153

DOI: 10.1083/jcb.145.1.153

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