Phosphatidylinositol(4,5)-bisphosphate [PI(4,5)P2] regulates cell adhesion and actin dynamics during cell migration. PI(4,5)P2 binds various components of the cell adhesion machinery, but how these processes affect migration of the epithelial cell sheet is not well understood. Here, we report that PI(4,5)P2 and Sktl, the kinase that converts PI4P to PI(4,5)P2, are both localized to the rear side of cells during wound healing of the Drosophila larval epidermis. The Sktl localization requires JNK pathway activation and integrins, but not PVR. The sktl knockdown epidermis displays strong defects in would closure, reminiscent of the JNK-depleted epidermis, and shows severe disruption of cell polarity, as determined by myosin II localization. Sktl and βPS integrin colocalize at the rear side of cells forming the trailing edge during wound healing and the two are inter-dependent in that the absence of one severely disrupts the rear localization of the other. These results strongly suggest that the JNK pathway regulates the rear localization of Sktl and integrins and the interplay between Sktl and integrins sets up cell polarity, which is crucial for reepithelialisation during wound healing.
Bibliographical noteFunding Information:
We thank M. Galko, A. Guichet, D. Kiehart, J. Lippincott-Schwartz, M. Mavrakis, and S. Parkhurst for providing fly stocks and antibodies, and the Bloomington Stock Center, the National Institute of Genetics in Japan, and the Vienna Drosophila Resource Center for fly stocks. We also thank our colleagues in the Choe lab for helpful discussions. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government, Ministry of Science and ICT (2015R1A2A2A01006660 and 2019R1F1A1044593) to K.-M.C.
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