Ric-8A, an activator protein of Gαi, controls mammalian epithelial cell polarity for tight junction assembly and cystogenesis

Autor:	Hideki Sumimoto, Kanako Chishiki, Junya Hayase, Sachiko Kamakura
Rok vydání:	2017
Předmět:	0301 basic medicine Organogenesis Gi alpha subunit Mitosis Spindle Apparatus Biology GTP-Binding Protein alpha Subunits Gi-Go Madin Darby Canine Kidney Cells Tight Junctions 03 medical and health sciences Dogs Mutant protein Genetics Animals Guanine Nucleotide Exchange Factors Epithelial polarity Tight junction Binding protein Cell Polarity Epithelial Cells Cell Biology Apical membrane Cell biology Spindle apparatus Protein Transport 030104 developmental biology Heterotrimeric G Protein Subunit
Zdroj:	Genes to cells : devoted to molecularcellular mechanisms. 22(3)
ISSN:	1365-2443
Popis:	Correct cyst morphogenesis of epithelial cells requires apical-basal polarization, which is partly regulated by mitotic spindle orientation, a process dependent on the heterotrimeric G protein subunit Gαi and its binding protein LGN. Here, we show that in three-dimensional culture of mammalian epithelial Madin-Darby canine kidney (MDCK) cells, the Gαi-activating protein Ric-8A is crucial for orientation of the mitotic spindle and formation of normal cysts that comprise a single layer of polarized cells with their apical surfaces lining an inner lumen. Consistent with the involvement of LGN, cystogenesis can be well organized by ADP-ribosylated Gαi, retaining the ability to interact with LGN, but not by the interaction-defective mutant protein Gαi2 (N150I). In monolayer culture of MDCK cells, functional tight junction (TJ) assembly, a process associated with epithelial cell polarization, is significantly delayed in Ric-8A-depleted cells as well as in Gαi-depleted cells in a mitosis-independent manner. Ric-8A knockdown results in a delayed cortical delivery of Gαi and the apical membrane protein gp135, and an increased formation of intercellular lumens surrounded by membranes rich in Gαi3 and gp135. TJ development also involves LGN and its related protein AGS3. Thus, Ric-8A regulates mammalian epithelial cell polarity for TJ assembly and cystogenesis probably in concert with Gαi and LGN/AGS3.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6184464269bf9c11b5ee5271d6473dc6 https://pubmed.ncbi.nlm.nih.gov/28185378 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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