RRC ID 57134
Author Tsarouhas V, Liu D, Tsikala G, Fedoseienko A, Zinn K, Matsuda R, Billadeau DD, Samakovlis C.
Title WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis.
Journal Nat Commun
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.
Volume 10(1)
Pages 2193
Published 2019-5-16
DOI 10.1038/s41467-019-10229-6
PII 10.1038/s41467-019-10229-6
PMID 31097705
PMC PMC6522504
MeSH Actins / metabolism Animals Animals, Genetically Modified Cell Line Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster Embryo, Nonmammalian / diagnostic imaging Endosomes / metabolism* Epithelium / diagnostic imaging Epithelium / growth & development Fibroblasts Intravital Microscopy Mice Microfilament Proteins / genetics Microfilament Proteins / metabolism Microscopy, Confocal Morphogenesis / physiology* Phosphorylation / physiology Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Receptor-Like Protein Tyrosine Phosphatases, Class 4 / genetics Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism Respiratory System / diagnostic imaging Respiratory System / growth & development Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism*
IF 11.878
Times Cited 1
Drosophila DGRC#102398