Phosphorylation of GMFγ by c-Abl Coordinates Lamellipodial and Focal Adhesion Dynamics to Regulate Airway Smooth Muscle Cell Migration

American Journal of Respiratory Cell and Molecular Biology
Brennan D GerlachDale D Tang

Abstract

Airway smooth muscle cells require coordinated protrusion and focal adhesion dynamics to migrate properly. However, the signaling cascades that connect these two processes remain incompletely understood. Glia maturation factor (GMF)-γ has been implicated in inducing actin debranching and inhibiting nucleation. In this study, we discovered that GMFγ phosphorylation at Y104 regulates human airway smooth muscle cell migration. Using high-resolution microscopy coupled with three-dimensional object-based quantitative image analysis software, Imaris 9.2.0, phosphomimetic mutant, Y104D-GMFγ, was enriched at nascent adhesions along the leading edge where it recruited activated neural Wiskott-Aldrich syndrome protein (N-WASP; pY256) to promote actin-branch formation, which enhanced lamellipodial dynamics and limited the growth of focal adhesions. Unexpectedly, we found that nonphosphorylated mutant, Y104F-GMFγ, was enriched in growing adhesions where it promoted a linear branch organization and focal adhesion clustering, and recruited zyxin to increase maturation, thus inhibiting lamellipodial dynamics and cell migration. The localization of GMFγ between the leading edge and focal adhesions was dependent upon myosin activity. Furthermor...Continue Reading

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Citations

Apr 6, 2019·American Journal of Respiratory Cell and Molecular Biology·Mark D Ihrie, Jennifer L Ingram
Sep 12, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shi PanDeepak A Deshpande
Apr 28, 2020·American Journal of Respiratory and Critical Care Medicine·Sejal SaglaniAdnan Custovic
Jun 4, 2021·Journal of Asthma and Allergy·Anne Chetty, Heber C Nielsen
Aug 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yinna WangDale D Tang

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Methods Mentioned

BETA
co-IP
Transfection
confocal microscopy

Software Mentioned

NIH ImageJ
GraphPad
Airyscan
GraphPad Prism
Imaris
MatLab
ImageJ
Filament Tracer
Image J
IQTL

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