RRC ID 48780
著者 Oguchi ME, Noguchi K, Fukuda M.
タイトル TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells.
ジャーナル PLoS One
Abstract Recycling endosomes are generally thought to play a central role in endocytic recycling, but recent evidence has indicated that they also participate in other cellular events, including cytokinesis, autophagy, and neurite outgrowth. Rab small GTPases are key regulators in membrane trafficking, and although several Rab isoforms, e.g., Rab11, have been shown to regulate recycling endosomal trafficking, the precise mechanism by which these Rabs regulate recycling endosomes is not fully understood. In this study, we focused on a Rab-GTPase-activating protein (Rab-GAP), one of the key regulators of Rabs, and comprehensively screened 43 mammalian Tre-2/Bub2/Cdc16 (TBC)/Rab-GAP-domain-containing proteins (TBC proteins) for proteins that specifically localize on recycling endosomes in mouse embryonic fibroblasts (MEFs). Four of the 43 mammalian TBC proteins screened, i.e., TBC1D11, TBC1D12, TBC1D14, and EVI5, were found to colocalize well with transferrin receptor, a well-known recycling endosome marker. We further investigated the biochemical properties of TBC1D12, a previously uncharacterized TBC protein. The results showed that TBC1D12 interacted with active Rab11 through its middle region and that it did not display Rab11-GAP activity in vitro. The recycling endosomal localization of TBC1D12 was found to depend on the expression of Rab11. We also found that TBC1D12 expression had no effect on common Rab11-dependent cellular events, e.g., transferrin recycling, in MEFs and that it promoted neurite outgrowth, a specialized Rab11-dependent cellular event, of PC12 cells independently of its GAP activity. These findings indicated that TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells.
巻・号 12(4)
ページ e0174883
公開日 2017-4-6
DOI 10.1371/journal.pone.0174883
PII PONE-D-16-47142
PMID 28384198
PMC PMC5383037
MeSH Animals Cells, Cultured GTP-Binding Proteins / metabolism* GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism GTPase-Activating Proteins / physiology* Gene Knockdown Techniques Mice Neuronal Outgrowth / physiology* PC12 Cells Rats
IF 2.74
引用数 5
WOS 分野 CELL BIOLOGY
リソース情報
遺伝子材料 pEF-T7-human TBC1D12-N (RDB14979) pEF-T7-human TBC1D12-M (RDB14980) pEF-T7-human TBC1D12-TBC (RDB14981) pEGFP-C1-human TBC1D12-R559K (RDB14999) pEGFP-C1-human TBC1D28 (RDB15015) pEGFP-C1-human TBC1D29 (RDB15016) pGEX-4T-3-mouse Rab11A-Q70L (RDB15028) pGEX-4T-3-mouse Rab11A-S25N (RDB15029) pmStr-C1-mouse Rab11A (RDB15030) pmStr-C1-mouse Rab11A-Q70L (RDB15031) pmStr-C1-mouse Rab11A-S25N (RDB15032)