WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis

Vasilios Tsarouhas, Dan Liu, Georgia Tsikala, Alina Fedoseienko, Kai Zinn, Ryo Matsuda, Daniel D. Billadeau and Christos Samakovlis ()
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Vasilios Tsarouhas: The Wenner-Gren Institute, Stockholm University
Dan Liu: The Wenner-Gren Institute, Stockholm University
Georgia Tsikala: The Wenner-Gren Institute, Stockholm University
Alina Fedoseienko: College of Medicine, Mayo Clinic
Kai Zinn: California Institute of Technology
Ryo Matsuda: The Wenner-Gren Institute, Stockholm University
Daniel D. Billadeau: College of Medicine, Mayo Clinic
Christos Samakovlis: The Wenner-Gren Institute, Stockholm University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10229-6

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