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Control of rapsyn stability by the CUL-3-containing E3 ligase complex
- Title
- Control of rapsyn stability by the CUL-3-containing E3 ligase complex
- Authors
- Nam S.; Min K.; Hwang H.; Lee H.-O.; Lee J.H.; Yoon J.; Lee H.; Park S.; Lee J.
- Ewha Authors
- 박성수
- SCOPUS Author ID
- 박성수
- Issue Date
- 2009
- Journal Title
- Journal of Biological Chemistry
- ISSN
- 0021-9258
- Citation
- Journal of Biological Chemistry vol. 284, no. 12, pp. 8195 - 8206
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Rapsyn is a postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. Here we report the mechanism for posttranslational control of rapsyn protein stability. We confirmed that C18H9.7-encoded RPY-1 is a rapsyn homolog in Caenorhabditis elegans by showing that human rapsyn rescued rpy-1 mutant phenotypes in nematodes, as determined by levamisole assays and micropost array behavioral assays. We found that RPY-1 was degraded in the absence of functional UNC-29, a non-α subunit of the receptor, in an allele-specific manner, but not in the absence of other receptor subunits. The cytoplasmic loop of UNC-29 was found to be critical for RPY-1 stability. Through RNA interference screening, we found that UBC-1, UBC-12, NEDD-8, and RBX-1 were required for degradation of RPY-1. We identified cullin (CUL)-3 as a component of E3 ligase and KEL-8 as the substrate adaptor of RPY-1. Mammalian rapsyn was ubiquitinated by the CUL3/KLHL8-containing E3 ligase in vitro, and the knockdown of KLHL-8, a mammalian KEL-8 homolog, inhibited rapsyn ubiquitination in vivo, implying evolutionary conservation of the rapsyn stability control machinery. kel-8 suppression and rpy-1 overexpression in C. elegans produced a phenotype similar to that of a loss-of-function mutation of rpy-1, suggesting that control of rapsyn abundance is important for proper function of the receptor. Our results suggest a link between the control of rapsyn abundance and congenital myasthenic syndromes. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
- DOI
- 10.1074/jbc.M808230200
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
- Files in This Item:
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