期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9128
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资金
- Deutsche Forschungsgemeinschaft [EB 160/4-1, EB 160/4-2, GE 514/9-1]
- Medical Faculty of the University Munster (IZKF) [Eb2/028/09]
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.
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