Regulation and Tuning of Smooth Muscle Myosin

Abstract

Smooth muscle myosin is regulated by phosphorylation of one of the two myosin light chains. This phosphorylation causes an unfolding of the myosin that allows it to interact with actin to produce force. The inactive state involves trapping the myosin in a conformation wherein the myosin heads interact with a segment of the myosin rod. Phosphorylation of the regulatory light chain weakens these interactions and allows the myosin to be activated. Smooth muscle myosin has a large movement of its light chain binding domain that is coupled to ADP release. This structural change may be necessary for the generation of "latch." Smooth muscle myosin has three different regions that vary to generate different isoforms: (1) an alternative insertion within the myosin head; (2) two possible essential light chains; and (3) an alternative tail at the end of the myosin rod. There is substantial evidence that the insertion in the myosin head increases the enzymatic activity of the myosin and leads to greater shortening velocity. The function of the other two variants is as yet unclear.

Cross-linking of actin filaments by myosin II is a major contributor to cortical integrity and cell motility in restrictive environments

“…This result is consistent with rheological measurements that show that mixing myosin II with actin filaments in the presence of ADP can dramatically stiffen the matrix (Humphrey et al, 2002). How the cell might regulate this aspect of myosin function is unknown, but a precedent exists in the latch state of smooth muscle myosin where force production is not always directly linked to actin binding (Sweeney, 1998).…”

“…This result is consistent with rheological measurements that show that mixing myosin II with actin filaments in the presence of ADP can dramatically stiffen the matrix (Humphrey et al, 2002). How the cell might regulate this aspect of myosin function is unknown, but a precedent exists in the latch state of smooth muscle myosin where force production is not always directly linked to actin binding (Sweeney, 1998).We, and others have previously shown that cells lacking myosin II are unable to accomplish morphogenetic movements (Clow and McNally, 1999;Shelden and Knecht, 1995). In aggregation streams the mhcA -cells were unable to move amidst the mass of adhered cells and became dramatically stretched as they tried to make and break contacts with neighboring cells in this environment .…”

The Essential Light Chain N-terminal Extension Alters Force and Fiber Kinetics in Mouse Cardiac Muscle

“…Muscle myosin (myosin II) is a hexamer that contains two heavy chains (MHCs), 3 with each heavy chain having two types of light chains:…”

“…Both myosin light chains are involved in stabilizing the lever arm, the long ␣-helix extending from the catalytic motor part of the myosin head to the coiled-coil backbone. Most regulatory light chains modulate the interaction of the myosin head with actin through phosphorylation of residues near the N terminus (1)(2)(3)(4)(5)(6)(7). In contrast, most ELCs are believed to modulate myosin head-actin interaction through direct binding of an N-terminal extension to actin (8 -14).…”

α1 adrenergic receptor agonist, phenylephrine, actively contracts early rat rib fracture callus ex vivo

“…8 Contraction of smooth muscle and nonmuscle cells such as myofibroblasts is generally activated by pharmacomechanical coupling mechanisms, which, via different complex pathways, regulate the myosin light chain kinase/myosin phosphatase ratio and thus the degree of myosin and actin interaction. [9][10][11][12] Various smooth muscle effectors including the a 1 adrenergic receptor (a 1 AR) agonist noradrenaline, 13 nerve growth factor, 14 galanin, 15 and nitric oxide 16 are up-regulated during early stages of fracture healing. It is suggested that these effectors may play a role in regulating the contractile state of early callus that may influence healing.…”