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, Christos Samakovlis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2193
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

phosphorylation
Phosphorylation
Morphogenesis
integrity
Actins
tyrosine
bundles
proteins
Drosophila
shape control
phosphatases
locomotion
mutations
division
mice
assembly
nucleation
tubes
defects
polarization

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Tsarouhas, V., Liu, D., Tsikala, G., Fedoseienko, A., Zinn, K., Matsuda, R., ... Samakovlis, C. (2019). WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis. Nature communications, 10(1), [2193]. https://doi.org/10.1038/s41467-019-10229-6

WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis. / Tsarouhas, Vasilios; Liu, Dan; Tsikala, Georgia; Fedoseienko, Alina; Zinn, Kai; Matsuda, Ryo; Billadeau, Daniel D; Samakovlis, Christos.

In: Nature communications, Vol. 10, No. 1, 2193, 01.12.2019.

Research output: Contribution to journalArticle

Tsarouhas, Vasilios ; Liu, Dan ; Tsikala, Georgia ; Fedoseienko, Alina ; Zinn, Kai ; Matsuda, Ryo ; Billadeau, Daniel D ; Samakovlis, Christos. / WASH phosphorylation balances endosomal versus cortical actin network integrities during epithelial morphogenesis. In: Nature communications. 2019 ; Vol. 10, No. 1.
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