Regulation of smooth muscle actin-myosin interaction and force by calponin.
Smooth muscle contraction is regulated primarily by the reversible phosphorylation of myosin triggered by an increase in sarcoplasmic free Ca2+ concentration ([Ca2+]i). Contraction can, however, be modulated by other signal transduction pathways, one of which involves the thin filament-associated protein calponin. The h1 (basic) isoform of calponin binds to actin with high affinity and is expressed specifically in smooth muscle at a molar ratio to actin of 1:7. Calponin inhibits (i) the actin-activated MgATPase activity of smooth muscle myosin (the cross-bridge cycling rate) via its interaction with actin, (ii) the movement of actin filaments over immobilized myosin in the in vitro motility assay, and (iii) force development or shortening velocity in permeabilized smooth muscle strips and single cells. These inhibitory effects of calponin can be alleviated by protein kinase C (PKC)-catalysed phosphorylation and restored following dephosphorylation by a type 2A phosphatase. Three physiological roles of calponin can be considered based on its in vitro functional properties: (i) maintenance of relaxation at resting [Ca2+]i, (ii) energy conservation during prolonged contractions, and (iii) Ca(2+)-independent contraction mediated by phosphorylation of calponin by PKC epsilon, a Ca(2+)-independent isoenzyme of PKC.
Winder
S J
SJ
Smooth Muscle Research Group, University of Calgary, Alberta, Canada.
Allen
B G
BG
Clément-Chomienne
O
O
Walsh
M P
MP
D000199:Actins / Q000737:chemistry / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000096985:Calponins
D000199:Actins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009218:Myosins; D000096985:Calponins