Regulation of the cross-bridge cycle: the effects of MgADP, LC17 isoforms and telokin.
This review summarizes the role of MgADP in force maintenance by dephosphorylated cross-bridges in smooth muscle and a potential physiological role for telokin. In tonic, compared with phasic, smooth muscles the affinity of cross-bridges in approximately 5 times higher for MgADP and the apparent second-order rate constant for MgATP is approximately 3 times lower. This gives rise to a large population of dephosphorylated cross-bridges in tonic smooth muscle. Such cross-bridges are thought to be major determinants of the different relaxation kinetics of the two types of smooth muscle and contribute to force maintenance at low levels of MLC20 phosphorylation, termed 'catch-like state' (Somlyo & Somlyo 1967) or 'latch' (Dillon et al. 1981). The molecular basis of the different affinities for MgADP and MgATP between tonic and phasic smooth muscle myosin was explored by exchange of essential myosin light chain (LC17) isoforms. In phasic bladder smooth muscle the exchange of LC17b for LC17a caused a significant decrease in the unloaded shortening velocity of non-phosphorylated, slowly cycling cross-bridges, suggesting that the LC17 isoforms contribute to the nucleotide affinity of latch bridges. The role of telokin in Ca(2+)-desensitization in phasic smooth muscle is reviewed. Telokin, the independently expressed C-terminus of myosin light chain kinase, is extensively phosphorylated during forskolin- and 8-br-cGMP-induced relaxation in situ. Telokin accelerated dephosphorylation of the regulatory myosin light chain and relaxed rabbit ileum smooth muscle. The results suggest that telokin contributes to cAMP and/or cGMP kinase-mediated Ca(2+)-desensitization of phasic smooth muscles.
Somlyo
A V
AV
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Centre, Charlottesville 22906-0011, USA.
Matthew
J D
JD
Wu
X
X
Khromov
A S
AS
Somlyo
A P
AP
D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D006801:Humans; D007536:Isomerism; D009124:Muscle Proteins / Q000737:chemistry*; D018994:Myosin Light Chains / Q000737:chemistry*; D009219:Myosin-Light-Chain Kinase / Q000737:chemistry*; D010446:Peptide Fragments; D010455:Peptides; D010766:Phosphorylation; D011817:Rabbits
D009124:Muscle Proteins; D018994:Myosin Light Chains; D010446:Peptide Fragments; D010455:Peptides; C060640:telokin; D000244:Adenosine Diphosphate; D009219:Myosin-Light-Chain Kinase