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JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis

Author

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  • Hüseyin Tuncay

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster)

  • Benjamin F. Brinkmann

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster
    Interdisciplinary Clinical Research Center (IZKF), University of Münster)

  • Tim Steinbacher

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster)

  • Annika Schürmann

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster)

  • Volker Gerke

    (Institute of Medical Biochemistry, ZMBE, University of Münster
    Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster)

  • Sandra Iden

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster
    Present address: Cologne Excellence Cluster CECAD, University Hospital Cologne, 50931 Cologne, Germany)

  • Klaus Ebnet

    (Institute-Associated Research Group ‘Cell Adhesion and Cell Polarity’, University of Münster
    Institute of Medical Biochemistry, ZMBE, University of Münster
    Interdisciplinary Clinical Research Center (IZKF), University of Münster)

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.

Suggested Citation

  • Hüseyin Tuncay & Benjamin F. Brinkmann & Tim Steinbacher & Annika Schürmann & Volker Gerke & Sandra Iden & Klaus Ebnet, 2015. "JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9128
    DOI: 10.1038/ncomms9128
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