title: SHIP2 Regulates Lumen Generation, Cell Division, and Ciliogenesis through the Control of Basolateral to Apical Lumen Localization of Aurora A and HEF 1.
abstract: Lumen formation during epithelial morphogenesis requires the creation of a luminal space at cell interfaces named apical membrane-initiation sites (AMISs). This is dependent upon integrated signaling from mechanical and biochemical cues, vesicle trafficking, cell division, and processes tightly coupled to ciliogenesis. Deciphering relationships between polarity determinants and lumen or cilia generation remains a fundamental issue. Here, we report that Src homology 2 domain-containing inositol 5-phosphatase 2 (SHIP2), a basolateral determinant of polarity, regulates RhoA-dependent actin contractility and cell division to form AMISs. SHIP2 regulates mitotic spindle alignment. SHIP2 is expressed in G1 phase, whereas Aurora A kinase is enriched in mitosis. SHIP2 binds Aurora A kinase and the scaffolding protein HEF1 and promotes their basolateral localization at the expense of their luminal expression connected with cilia resorption. Furthermore, SHIP2 expression increases cilia length. Thus, our findings offer new insight into the relationships among basolateral proteins, lumen generation, and ciliogenesis.
authors.affiliation: Université Paris-Sud, 91400 Orsay, France; Unité 1193, 94800 Villejuif, France.
authors.forename: Ola
authors.initials: O
authors.lastname: Hamze-Komaiha
authors.affiliation: Université Paris-Sud, 91400 Orsay, France; Unité 1193, 94800 Villejuif, France.
authors.forename: Sokavuth
authors.initials: S
authors.lastname: Sarr
authors.affiliation: IGDR-UMR CNRS 6290, Faculté de Médecine, Université de Rennes 1, 35000 Rennes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.affiliation: Université Paris-Sud, 91400 Orsay, France; Unité 1193, 94800 Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, 94800 Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Université Paris-Sud, 91400 Orsay, France; Unité 1193, 94800 Villejuif, France. Electronic address: ama.gassama@inserm.fr.
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D016764:Cell Polarity; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D009024:Morphogenesis / Q000235:genetics*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010750:Phosphoproteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D020742:rhoA GTP-Binding Protein
keywords: AMIS; Aurora A; HEF1; SHIP2; apico-basal polarity; cell division; cell polarity; ciliogenesis; lumen formation; phosphoinositides