Regulation of Myosin Light-Chain Phosphatase Activity to Generate Airway Smooth Muscle Hypercontractility.

Mayra D Álvarez-Santos,Blanca Bazán-Perkins,Marisol Álvarez-González,Samuel Estrada-Soto

doi:10.3389/fphys.2020.00701

Abstract

Smooth muscle is a central structure involved in the regulation of airway tone. In addition, it plays an important role in the development of some pathologies generated by alterations in contraction, such as hypercontractility and the airway hyperresponsiveness observed in asthma. The molecular processes associated with smooth muscle contraction are centered around myosin light chain (MLC) phosphorylation, which is controlled by a balance in the activity of myosin light-chain kinase (MLCK) and myosin light-chain phosphatase (MLCP). MLCK activation depends on increasing concentrations of intracellular Ca2+, while MLCP activation is independent of Ca2+. MLCP contains a phosphatase subunit (PP1c) that is regulated through myosin phosphatase target subunit 1 (MYPT1) and other subunits, such as glycogen-associated regulatory subunit and myosin-binding subunit 85 kDa. Interestingly, MLCP inhibition may contribute to exacerbation of smooth muscle contraction by increasing MLC phosphorylation to induce hypercontractility. Many pathways inhibiting MLCP activity in airway smooth muscle have been proposed and are focused on inhibition of PP1c, inhibitory phosphorylation of MYPT1 and dissociation of the PP1c-MYPT1 complex.

Highlights

Kinases and phosphatases are key regulatory components of many cellular processes
Inhibition of MLC20 dephosphorylation reflects the decrease in myosin light-chain phosphatase (MLCP) activity (Ojiaku et al, 2018; Shaifta et al, 2018) and is a thought-provoking perspective that we review to explain the hypercontractility of airway smooth muscle
myosin phosphatase target subunit 1 (MYPT1) phosphorylation at the Ser507, Thr853/850, and Thr696/695 residues mediates the inhibition of MLCP activity and the inhibition of airway smooth muscle relaxation

Summary

Introduction

Kinases and phosphatases are key regulatory components of many cellular processes. Mathematical analysis of kinase–phosphatase pathways suggests that kinases have an important role in modulating the signal amplitude, while phosphatases control the duration of responses (Heinrich et al, 2002). MYPT1 phosphorylation at the Ser507, Thr853/850, and Thr696/695 residues mediates the inhibition of MLCP activity and the inhibition of airway smooth muscle relaxation.

Results

Conclusion