Over expression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells

Han, Hong, Noakes, Peter G. and Phillips, William D. (1999) Over expression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells. Journal of neurocytology, 28 9: 763-775. doi:10.1023/A:1007098406748


Author Han, Hong
Noakes, Peter G.
Phillips, William D.
Title Over expression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells
Journal name Journal of neurocytology   Check publisher's open access policy
ISSN 0300-4864
1573-7381
Publication date 1999-09-01
Sub-type Article (original research)
DOI 10.1023/A:1007098406748
Volume 28
Issue 9
Start page 763
End page 775
Total pages 13
Place of publication London
Publisher Kluwer
Language eng
Subject 060110 Receptors and Membrane Biology
060805 Animal Neurobiology
Abstract Rapsyn is a protein on the cytoplasmic face of the postsynaptic membrane of skeletal muscle that is essential for clustering acetylcholine receptors (AChR). Here we show that transfection of rapsyn cDNA can restore AChR clustering function to muscle cells cultured from rapsyn deficient (KORAP) mice. KORAP myotubes displayed no AChR aggregates before or after treatment with neural agrin. After transfection with rapsyn expression plasmid, some KORAP myotubes expressed rapsyn at physiological levels. These formed large AChR-rapsyn clusters in response to agrin, just like wild-type myotubes. KORAP myotubes that overexpressed rapsyn formed only scattered AChR-rapsyn microaggregates, irrespective of agrin treatment. KORAP cells were then transfected with mutant forms of rapsyn. A deletion mutant lacking residues 16–254 formed rapsyn microaggregates, but failed to aggregate AChRs. Substitution mutation to the C-terminal serine phosphorylation site of rapsyn (M43D405,D406) did not impair the response to agrin, showing that differential phosphorylation of this site is unlikely to mediate agrin-induced clustering. The results indicate that rapsyn expression is essential for agrin-induced AChR clustering but that its overexpression inhibits this pathway. The approach of using rapsyn-deficient muscle cells opens the way for defining the role of rapsyn in agrin-induced AChR clustering.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 19 May 2009, 22:15:58 EST by Ms Lynette Adams on behalf of School of Biomedical Sciences