TRIM50 Regulates Vesicular Trafficking for Acid Secretion in Gastric Parietal Cells
| Autor: | Fumihiko Kisa, Miyuki Nishi, Hiroshi Takeshima, Mingzhai Sun, Hua Zhu, Pei-Hui Lin, Bo Van, Fumiyo Aoyama, Jianjie Ma, Akira Sawaguchi |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0303 health sciences
Vesicle Biophysics Biology Bone canaliculus Cell biology Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry Gastric mucosa medicine Gastric acid Secretion Phosphatidylinositol 030217 neurology & neurosurgery Actin 030304 developmental biology |
| Zdroj: | Biophysical Journal. (2):292a |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2012.11.1632 |
| Popis: | Within the human genome, there are ∼80 members of the tri-partite motif (TRIM) family proteins. Our previous studies have defined MG53, a muscle-specific TRIM protein, as an essential component of the cell membrane repair machinery. Sequence homology analysis reveals a strong sequence similarity between MG53 and TRIM50 - a stomach-specific TRIM member whose biological function has yet to be defined. Our biochemical data demonstrated that TRIM50 is specifically expressed in gastric parietal cells, and 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-knockout 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. |
| Databáze: | OpenAIRE |
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