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Nat Commun. 2019 May 16;10(1):2193. doi: 10.1038/s41467-019-10229-6.

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

Author information

1
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden.
2
SciLifeLab, SE-171 65, Stockholm, Sweden.
3
Department of Biochemistry and Division of Oncology Research, College of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
4
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
5
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden. Christos.Samakovlis@su.se.
6
SciLifeLab, SE-171 65, Stockholm, Sweden. Christos.Samakovlis@su.se.
7
Cardiopulmonary Institute, Justus Liebig University of Giessen, Aulweg 130, Giessen, 35392, Germany. Christos.Samakovlis@su.se.

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.

PMID:
31097705
PMCID:
PMC6522504
DOI:
10.1038/s41467-019-10229-6
[Indexed for MEDLINE]
Free PMC Article

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