title: JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis.
abstract: Planar spindle orientation in polarized epithelial cells depends on the precise localization of the dynein-dynactin motor protein complex at the lateral cortex. The contribution of cell adhesion molecules to the cortical localization of the dynein-dynactin complex is poorly understood. Here we find that junctional adhesion molecule-A (JAM-A) regulates the planar orientation of the mitotic spindle during epithelial morphogenesis. During mitosis, JAM-A triggers a transient activation of Cdc42 and PI(3)K, generates a gradient of PtdIns(3,4,5)P3 at the cortex and regulates the formation of the cortical actin cytoskeleton. In the absence of functional JAM-A, dynactin localization at the cortex is reduced, the mitotic spindle apparatus is misaligned and epithelial morphogenesis in three-dimensional culture is compromised. Our findings indicate that a PI(3)K- and cortical F-actin-dependent pathway of planar spindle orientation operates in polarized epithelial cells to regulate epithelial morphogenesis, and we identify JAM-A as a junctional regulator of this pathway.
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.
authors: Hüseyin
authors: H
authors: Tuncay
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.|Interdisciplinary Clinical Research Center (IZKF), University of Münster, 48149 Münster, Germany.
authors: Benjamin F
authors: BF
authors: Brinkmann
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.
authors: Tim
authors: T
authors: Steinbacher
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.
authors: Annika
authors: A
authors: Schürmann
authors: Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Münster, 48149 Münster, Germany.
authors: Volker
authors: V
authors: Gerke
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.
authors: Sandra
authors: S
authors: Iden
authors: Institute-Associated Research Group 'Cell Adhesion and Cell Polarity', University of Münster, 48149 Münster, Germany.|Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany.|Interdisciplinary Clinical Research Center (IZKF), University of Münster, 48149 Münster, Germany.
authors: Klaus
authors: K
authors: Ebnet
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D004285:Dogs; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D062745:Junctional Adhesion Molecule A / Q000235:genetics* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D000072159:Dynactin Complex; D062745:Junctional Adhesion Molecule A; D008869:Microtubule-Associated Proteins; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D019869:Phosphatidylinositol 3-Kinases; D004398:Dyneins; D020764:cdc42 GTP-Binding Protein