Phosphorylation of GMFG by c-Abl coordinates lamellipodial and focal adhesion dynamics to regulate airway smooth muscle cell migration

Research output: Contribution to journalArticle

Authors

  • Brennan D. Gerlach
  • Kate Tubbesing
  • Guoning Liao
  • Alyssa C. Rezey
  • Ruping Wang
  • Margarida Barroso
  • Dale D. Tang

External Institution(s)

  • Albany Medical College

Details

Original languageEnglish (US)
Pages (from-to)219-231
Number of pages13
JournalAmerican journal of respiratory cell and molecular biology
Volume61
Issue number2
StatusPublished - Aug 1 2019
Peer-reviewedYes

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)-g has been implicated in inducing actin debranching and inhibiting nucleation. In this study, we discovered that GMFg 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-GMFg, 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-GMFg, 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 GMFg between the leading edge and focal adhesions was dependent upon myosin activity. Furthermore, c-Abl tyrosine kinase regulated the GMFg phosphorylation–dependent processes. Together, these results unveil the importance of GMFg phosphorylation in coordinating lamellipodial and focal adhesion dynamics to regulate cell migration.

    Research areas

  • Actin cytoskeleton, Airway smooth muscle, Cell migration, Protein phosphorylation

Citation formats

APA

Gerlach, B. D., Tubbesing, K., Liao, G., Rezey, A. C., Wang, R., Barroso, M., & Tang, D. D. (2019). Phosphorylation of GMFG by c-Abl coordinates lamellipodial and focal adhesion dynamics to regulate airway smooth muscle cell migration. American journal of respiratory cell and molecular biology, 61(2), 219-231. https://doi.org/10.1165/rcmb.2018-0352OC

Harvard

Gerlach, BD, Tubbesing, K, Liao, G, Rezey, AC, Wang, R, Barroso, M & Tang, DD 2019, 'Phosphorylation of GMFG by c-Abl coordinates lamellipodial and focal adhesion dynamics to regulate airway smooth muscle cell migration', American journal of respiratory cell and molecular biology, vol. 61, no. 2, pp. 219-231. https://doi.org/10.1165/rcmb.2018-0352OC