RRC ID 45944
著者 Chen C, Itakura E, Weber KP, Hegde RS, de Bono M.
タイトル An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism.
ジャーナル PLoS Genet
Abstract Despite the importance of G-protein coupled receptors (GPCRs) their biogenesis is poorly understood. Like vertebrates, C. elegans uses a large family of GPCRs as chemoreceptors. A subset of these receptors, such as ODR-10, requires the odr-4 and odr-8 genes to be appropriately localized to sensory cilia. The odr-4 gene encodes a conserved tail-anchored transmembrane protein; the molecular identity of odr-8 is unknown. Here, we show that odr-8 encodes the C. elegans ortholog of Ufm1-specific protease 2 (UfSP2). UfSPs are cysteine proteases identified biochemically by their ability to liberate the ubiquitin-like modifier Ufm1 from its pro-form and protein conjugates. ODR-8/UfSP2 and ODR-4 are expressed in the same set of twelve chemosensory neurons, and physically interact at the ER membrane. ODR-4 also binds ODR-10, suggesting that an ODR-4/ODR-8 complex promotes GPCR folding, maturation, or export from the ER. The physical interaction between human ODR4 and UfSP2 suggests that this complex's role in GPCR biogenesis may be evolutionarily conserved. Unexpectedly, mutant versions of ODR-8/UfSP2 lacking catalytic residues required for protease activity can rescue all odr-8 mutant phenotypes tested. Moreover, deleting C. elegans ufm-1 does not alter chemoreceptor traffic to cilia, either in wild type or in odr-8 mutants. Thus, UfSP2 proteins have protease- and Ufm1-independent functions in GPCR biogenesis.
巻・号 10(3)
ページ e1004082
公開日 2014-3-1
DOI 10.1371/journal.pgen.1004082
PII PGENETICS-D-13-01562
PMID 24603482
PMC PMC3945108
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Chemoreceptor Cells / metabolism Cilia / genetics Cilia / metabolism Cysteine Endopeptidases / genetics* Cysteine Endopeptidases / metabolism Endoplasmic Reticulum / genetics Endoplasmic Reticulum / metabolism HeLa Cells Humans Mice Olfactory Receptor Neurons / metabolism Proteins / genetics* Receptors, G-Protein-Coupled / genetics* Receptors, G-Protein-Coupled / metabolism Receptors, Odorant / genetics* Receptors, Odorant / metabolism Smell / genetics
IF 5.175
引用数 15
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm5234 tm4878 tm4888