RRC ID 42916
著者 Takaya A, Kamio T, Masuda M, Mochizuki N, Sawa H, Sato M, Nagashima K, Mizutani A, Matsuno A, Kiyokawa E, Matsuda M.
タイトル R-Ras regulates exocytosis by Rgl2/Rlf-mediated activation of RalA on endosomes.
ジャーナル Mol Biol Cell
Abstract R-Ras is a Ras-family small GTPase that regulates various cellular functions such as apoptosis and cell adhesion. Here, we demonstrate a role of R-Ras in exocytosis. By the use of specific anti-R-Ras antibody, we found that R-Ras was enriched on both early and recycling endosomes in a wide range of cell lines. Using a fluorescence resonance energy transfer-based probe for R-Ras activity, R-Ras activity was found to be higher on endosomes than on the plasma membrane. This high R-Ras activity on the endosomes correlated with the accumulation of an R-Ras effector, the Rgl2/Rlf guanine nucleotide exchange factor for RalA, and also with high RalA activity. The essential role played by R-Ras in inducing high levels of RalA activity on the endosomes was evidenced by the short hairpin RNA (shRNA)-mediated suppression of R-Ras and by the expression of R-Ras GAP. In agreement with the reported role of RalA in exocytosis, the shRNA of either R-Ras or RalA was found to suppress calcium-triggered exocytosis in PC12 pheochromocytoma cells. These data revealed that R-Ras activates RalA on endosomes and that it thereby positively regulates exocytosis.
巻・号 18(5)
ページ 1850-60
公開日 2007-5-1
DOI 10.1091/mbc.e06-08-0765
PII E06-08-0765
PMID 17344481
PMC PMC1855010
MeSH Animals Base Sequence COS Cells Cell Line Chlorocebus aethiops Dogs Endosomes / metabolism* Exocytosis / physiology* Humans Mice PC12 Cells RNA Interference RNA, Small Interfering / genetics Rats Transcription Factors / genetics Transcription Factors / metabolism* rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism* ral GTP-Binding Proteins / antagonists & inhibitors ral GTP-Binding Proteins / genetics ral GTP-Binding Proteins / metabolism* ras Proteins / antagonists & inhibitors ras Proteins / genetics ras Proteins / metabolism*
IF 3.791
引用数 41
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞