TY - JOUR
T1 - TRIM50 protein regulates vesicular trafficking for acid secretion in gastric parietal cells
AU - Nishi, Miyuki
AU - Aoyama, Fumiyo
AU - Kisa, Fumihiko
AU - Zhu, Hua
AU - Sun, Mingzhai
AU - Lin, Peihui
AU - Ohta, Hiroya
AU - Van, Bo
AU - Yamamoto, Shinichiro
AU - Kakizawa, Sho
AU - Sakai, Hideki
AU - Ma, Jianjie
AU - Sawaguchi, Akira
AU - Takeshima, Hiroshi
PY - 2012/9/28
Y1 - 2012/9/28
N2 - Of the TRIM/RBCC family proteins taking part in a variety of cellular processes, TRIM50 is a stomach-specific member with no defined biological function. Our biochemical data demonstrated that TRIM50 is specifically expressed in gastric parietal cells and is predominantly localized in the tubulovesicular and canalicular membranes. In cultured cells ectopically expressing GFP-TRIM50, confocal microscopic imaging revealed dynamic movement of TRIM50-associated vesicles in a phosphoinositide 3-kinase-dependent manner. A protein overlay assay detected preferential binding of the PRY-SPRY domain from the TRIM50 C-terminal region to phosphatidylinositol species, suggesting that TRIM50 is involved in vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids. Trim50 knockout mice retained normal histology in the gastric mucosa but exhibited impaired secretion of gastric acid. In response to histamine, Trim50 knock-out parietal cells generated deranged canaliculi, swollen microvilli lacking actin filaments, and excess multilamellar membrane complexes. Therefore, TRIM50 seems to play an essential role in tubulovesicular dynamics, promoting the formation of sophisticated canaliculi and microvilli during acid secretion in parietal cells.
AB - Of the TRIM/RBCC family proteins taking part in a variety of cellular processes, TRIM50 is a stomach-specific member with no defined biological function. Our biochemical data demonstrated that TRIM50 is specifically expressed in gastric parietal cells and is predominantly localized in the tubulovesicular and canalicular membranes. In cultured cells ectopically expressing GFP-TRIM50, confocal microscopic imaging revealed dynamic movement of TRIM50-associated vesicles in a phosphoinositide 3-kinase-dependent manner. A protein overlay assay detected preferential binding of the PRY-SPRY domain from the TRIM50 C-terminal region to phosphatidylinositol species, suggesting that TRIM50 is involved in vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids. Trim50 knockout mice retained normal histology in the gastric mucosa but exhibited impaired secretion of gastric acid. In response to histamine, Trim50 knock-out parietal cells generated deranged canaliculi, swollen microvilli lacking actin filaments, and excess multilamellar membrane complexes. Therefore, TRIM50 seems to play an essential role in tubulovesicular dynamics, promoting the formation of sophisticated canaliculi and microvilli during acid secretion in parietal cells.
UR - http://www.scopus.com/inward/record.url?scp=84866914803&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.370551
DO - 10.1074/jbc.M112.370551
M3 - 学術論文
C2 - 22872646
AN - SCOPUS:84866914803
SN - 0021-9258
VL - 287
SP - 33523
EP - 33532
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -