1. SHIP2 Regulates Lumen Generation, Cell Division, and Ciliogenesis through the Control of Basolateral to Apical Lumen Localization of Aurora A and HEF 1
- Author
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Hamze-Komaiha, Ola, Sarr, Sokavuth, Arlot-Bonnemains, Yannick, Samuel, Didier, Gassama-Diagne, Ama, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hépato-biliaire - CHB [Paul Brousse, Paris], Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Association pour la Recherche sur le Cancer (ARC/SUBV/CKLQ6), la Ligue Contre le Cancer, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse
- Subjects
HEF1 ,Spindle Apparatus ,Madin Darby Canine Kidney Cells ,Dogs ,Morphogenesis ,Animals ,Humans ,Aurora A ,Cilia ,Phosphorylation ,Adaptor Proteins, Signal Transducing ,Aurora Kinase A ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Cell Polarity ,Gene Expression Regulation, Developmental ,Epithelial Cells ,phosphoinositides ,apico-basal polarity ,SHIP2 ,Phosphoproteins ,Actins ,AMIS ,Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases ,rhoA GTP-Binding Protein ,ciliogenesis ,lumen formation ,Cell Division ,HeLa Cells ,Signal Transduction - Abstract
International audience; 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.
- Published
- 2016