TY - JOUR
T1 - WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis
AU - Tsarouhas, Vasilios
AU - Liu, Dan
AU - Tsikala, Georgia
AU - Fedoseienko, Alina
AU - Zinn, Kai
AU - Matsuda, Ryo
AU - Billadeau, Daniel D.
AU - Samakovlis, Christos
N1 - Funding Information:
We would like to thank Maura Strigini, Marcos Gonzalez-Gaitan, Kazuo Emoto, Markus Affolter, Susan Parkhurst, the Bloomington Drosophila Stock Center, Kyoto Drosophila Stock Center, the Drosophila Genomics Resource Center (DGRC; IN) and the Developmental Studies Hybridoma Bank (DSHB; IA) for fly strains, clones and antibodies. We thank fly community that isolated, characterized or distributed mutants or antibodies. Special thanks to Flybase for the Drosophila genomic resources. We thank the Stockholm University Imaging Facility (IFSU). We thank members of the M. Mannervik, C. Samakovlis, Q. Dai and S. Åström laboratories for comments and support during the project, especially K. Senti, B. Arefin and Y. Zhang for constructs and strains and M. Björk for fly service. This work was funded by the Swedish Research Council and the Swedish Cancer Society to C.S. C.S. was supported by the German Research Foundation (DFG), grant KFO309 (project number 284237345). D.D.B. was supported by National Institutes of Health grant 1R01 DK107733.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Filamentous actin (F-actin) networks facilitate key processes like cell shape control, division, polarization and motility. The dynamic coordination of F-actin networks and its impact on cellular activities are poorly understood. We report an antagonistic relationship between endosomal F-actin assembly and cortical actin bundle integrity during Drosophila airway maturation. Double mutants lacking receptor tyrosine phosphatases (PTP) Ptp10D and Ptp4E, clear luminal proteins and disassemble apical actin bundles prematurely. These defects are counterbalanced by reduction of endosomal trafficking and by mutations affecting the tyrosine kinase Btk29A, and the actin nucleation factor WASH. Btk29A forms protein complexes with Ptp10D and WASH, and Btk29A phosphorylates WASH. This phosphorylation activates endosomal WASH function in flies and mice. In contrast, a phospho-mimetic WASH variant induces endosomal actin accumulation, premature luminal endocytosis and cortical F-actin disassembly. We conclude that PTPs and Btk29A regulate WASH activity to balance the endosomal and cortical F-actin networks during epithelial tube maturation.
AB - Filamentous actin (F-actin) networks facilitate key processes like cell shape control, division, polarization and motility. The dynamic coordination of F-actin networks and its impact on cellular activities are poorly understood. We report an antagonistic relationship between endosomal F-actin assembly and cortical actin bundle integrity during Drosophila airway maturation. Double mutants lacking receptor tyrosine phosphatases (PTP) Ptp10D and Ptp4E, clear luminal proteins and disassemble apical actin bundles prematurely. These defects are counterbalanced by reduction of endosomal trafficking and by mutations affecting the tyrosine kinase Btk29A, and the actin nucleation factor WASH. Btk29A forms protein complexes with Ptp10D and WASH, and Btk29A phosphorylates WASH. This phosphorylation activates endosomal WASH function in flies and mice. In contrast, a phospho-mimetic WASH variant induces endosomal actin accumulation, premature luminal endocytosis and cortical F-actin disassembly. We conclude that PTPs and Btk29A regulate WASH activity to balance the endosomal and cortical F-actin networks during epithelial tube maturation.
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U2 - 10.1038/s41467-019-10229-6
DO - 10.1038/s41467-019-10229-6
M3 - Article
C2 - 31097705
AN - SCOPUS:85065891923
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2193
ER -