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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Actins
  • Drosophila Proteins
  • Microfilament Proteins
  • Vesicular Transport Proteins
  • WASH protein, Drosophila
  • WASH protein, mouse
  • Protein-Tyrosine Kinases
  • Btk29A protein, Drosophila
  • Protein Tyrosine Phosphatases
  • Ptp10D protein, Drosophila
  • Ptp4E protein, Drosophila
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4