Journal article
Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex
The Journal of cell biology, Vol.145(1), pp.153-165
04/05/1999
DOI: 10.1083/jcb.145.1.153
PMCID: PMC2148225
PMID: 10189375
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 α-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG–SPN subcomplex.
Details
- Title: Subtitle
- Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex
- Creators
- Rachelle H Crosbie - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Connie S Lebakken - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Kathleen H Holt - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109David P Venzke - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Volker Straub - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Jane C Lee - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109R. Mark Grady - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Jeffery S Chamberlain - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Joshua R Sanes - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109Kevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Pediatrics and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.145(1), pp.153-165
- DOI
- 10.1083/jcb.145.1.153
- PMID
- 10189375
- PMCID
- PMC2148225
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 04/05/1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984068280302771
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