A novel role for RhoA GTPase in the regulation of airway smooth muscle contraction

Wenwu Zhang, Youliang Huang, Yidi Wu, Susan Gunst

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent studies have demonstrated a novel molecular mechanism for the regulation of airway smooth muscle (ASM) contraction by RhoA GTPase. In ASM tissues, both myosin light chain (MLC) phosphorylation and actin polymerization are required for active tension generation. RhoA inactivation dramatically suppresses agonist-induced tension development and completely inhibits agonist-induced actin polymerization, but only slightly reduces MLC phosphorylation. The inhibition of MLC phosphatase does not reverse the effects of RhoA inactivation on contraction or actin polymerization. Thus, RhoA regulates ASM contraction through its effects on actin polymerization rather than MLC phosphorylation. Contractile stimulation of ASM induces the recruitment and assembly of paxillin, vinculin, and focal adhesion kinase (FAK) into membrane adhesion complexes (adhesomes) that regulate actin polymerization by catalyzing the activation of cdc42 GTPase by the G-protein-coupled receptor kinase-interacting target (GIT) – p21-activated kinase (PAK) – PAK-interacting exchange factor (PIX) complex. Cdc42 is a necessary and specific activator of the actin filament nucleation activator, N-WASp. The recruitment and activation of paxillin, vinculin, and FAK is prevented by RhoA inactivation, thus preventing cdc42 and N-WASp activation.Weconclude that RhoA regulates ASM contraction by catalyzing the assembly and activation of membrane adhesome signaling modules that regulate actin polymerization, and that the RhoA-mediated assembly of adhesome complexes is a fundamental step in the signal transduction process in response to a contractile agonist.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume93
Issue number2
DOIs
StatePublished - Nov 19 2014

Fingerprint

GTP Phosphohydrolases
Muscle Contraction
Polymerization
Smooth Muscle
Actins
Myosin Light Chains
p21-Activated Kinases
Paxillin
Vinculin
Focal Adhesion Protein-Tyrosine Kinases
Phosphorylation
Myosin-Light-Chain Phosphatase
G-Protein-Coupled Receptor Kinases
Membranes
Actin Cytoskeleton
Signal Transduction
Muscles

Keywords

  • Actin polymerization
  • Adhesion junction
  • Cdc42
  • Myosin light chain phosphorylation
  • Paxillin
  • Vinculin

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

A novel role for RhoA GTPase in the regulation of airway smooth muscle contraction. / Zhang, Wenwu; Huang, Youliang; Wu, Yidi; Gunst, Susan.

In: Canadian Journal of Physiology and Pharmacology, Vol. 93, No. 2, 19.11.2014, p. 129-136.

Research output: Contribution to journalArticle

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