title: TRIM50 protein regulates vesicular trafficking for acid secretion in gastric parietal cells.
abstract: 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 knock-out 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Aoyama
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kisa
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Mingzhai
authors.initials: M
authors.lastname: Sun
authors.forename: Peihui
authors.initials: P
authors.lastname: Lin
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ohta
authors.forename: Bo
authors.initials: B
authors.lastname: Van
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000143:Acids / Q000737:chemistry*; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism*; D005786:Gene Expression Regulation; D008214:Lymphocytes / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D010295:Parietal Cells, Gastric / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000143:Acids; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C576756:TRIM50 protein, rat; D019869:Phosphatidylinositol 3-Kinases