Wound closure in the Drosophila larval epidermis mainly involves nonproliferative, endocyling epithelial cells. Consequently, it is largely mediated by cell growth and migration. We discovered that both cell growth and migration in Drosophila require the cochaperone-encoding gene cdc37. Larvae lacking cdc37 in the epidermis failed to close wounds, and the cells of the epidermis failed to change cell shape and polarize. Likewise, wound-induced cell growth was significantly reduced, and correlated with a reduction in the size of the cell nucleus. The c-Jun N-terminal kinase (JNK) pathway, which is essential for wound closure, was not typically activated in injured cdc37 knockdown larvae. In addition, JNK, Hep, Mkk4, and Tak1 protein levels were reduced, consistent with previous reports showing that Cdc37 is important for the stability of various client kinases. Protein levels of the integrin β subunit and its wound-induced protein expression were also reduced, reflecting the disruption of JNK activation, which is crucial for expression of integrin β during wound closure. These results are consistent with a role of Cdc37 in maintaining the stability of the JNK pathway kinases, thus mediating cell growth and migration during Drosophila wound healing.
Bibliographical noteFunding Information:
We thank J. Ng, Y. Miyata, N. Silverman, B. Stronach, M. Therrien, The Bloomington Stock Center, The National Institute of Genetics in Japan, and The Vienna Drosophila Resource Center for fly stocks and antibodies. We are also very grateful to our colleagues in the laboratory for helpful discussions. This work was supported by a National Research Foundation of Korea grant funded by the Korean Government, Ministry of Science and ICT (Grant no. 2015R1A2A2A01006660) to K.-M.C.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology