RRC ID 74509
著者 Nakashima S, Matsui T, Fukuda M.
タイトル Vps9d1 regulates tubular endosome formation through specific activation of Rab22A.
ジャーナル J Cell Sci
Abstract The small GTPase Rab22A is an important regulator of the formation of tubular endosomes, which are one of the types of recycling endosome compartments of the clathrin-independent endocytosis pathway. In order to regulate tubular endosome formation, Rab22A must be activated by a specific guanine-nucleotide-exchange factor (GEF); however, all of the GEFs that have been reported to exhibit Rab22A-GEF activity in vitro also activate Rab5A, an essential regulator of the clathrin-mediated endocytosis pathway, and no Rab22A-specific GEF has ever been identified. Here, we identified Vps9d1, a previously uncharacterized vacuolar protein sorting 9 (VPS9) domain-containing protein, as a novel Rab22A-GEF. The formation of tubular endosome structures was found to be severely impaired in Vps9d1-depleted HeLa cells, but Rab5A localization was unaffected. Expression of a constitutively active Rab22A mutant in Vps9d1-depleted HeLa cells restored tubular endosomes, but expression of a GEF-activity-deficient Vps9d1 mutant did not. Moreover, Vps9d1 depletion altered the distribution of clathrin-independent endocytosed cargos and impaired their recycling. Our findings indicate that Vps9d1 promotes tubular endosome formation by specifically activating Rab22A.
巻・号 136(6)
公開日 2023-3-15
DOI 10.1242/jcs.260522
PII 286994
PMID 36762583
MeSH Clathrin / metabolism Endocytosis / physiology Endosomes* / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism HeLa Cells Humans Protein Transport / physiology rab GTP-Binding Proteins* / genetics rab GTP-Binding Proteins* / metabolism
IF 4.573
リソース情報
遺伝子材料 pmStr-C1-Vps9d1 (RDB19825) pmStr-C1-Vps9d1-Y628A (YA) (RDB19826)
ヒト・動物細胞 COS-7(RCB0539)