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
|
Resource |
Drosophila |
DGRC#102398 |