Myosin light chain interactions

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

Inhibitor of F-actin-myosin interaction (inhibitor of F-actin-dependent activation of ATPase) Troponin system (Tpl) Unphosphorylated myosin light chain... 

Effect of protein-bound Ca TpC 4Ca antagonizes Tpl inhibition of F-actin-myosin interaction (allows F-actin activation of ATPase) Calmodulin 4Ca activates myosin light chain kinase that phosphorylates myosin p-light chain. The phosphorylated p-light chain no longer inhibits F-actin-myosin interaction (allows F-actin activation of ATPase). 

Figure 22.12 Regulation of actin-myosin interaction in smooth muscle via the light-chain kinase and phosphatase and effect on blood pressure. ions bind to calmodulin and the complex stimulates the conversion of inactive myosin light chain kinase (MLCK) to active MLCK which then phosphorylates the light chain. This results in activation of the cross-bridge cycle. The overall effect is vasoconstriction of the arteriole, which increases blood pressure.

Many of the biochemical and molecular events that are responsible for uterine smooth muscle contraction are the same as those that control other smooth muscle tissues (Fig. 62.1). Once uterine smooth muscle sensitivity has been augmented, actin and myosin must interact for contraction to occur. This interaction depends on the phosphorylation of the contractile proteins by the enzyme myosin light chain kinase (MLCK). This enzyme requires Ca++ and is active only when associated with calmodulin. Activation of the entire muscle contraction... 

Valouev lA, Urakov VN, Kochneva-Pervukhova NV, Smirnov VN, Ter-Avanesyan MD (2004) Translation termination factors function outside of translation yeast eRFl interacts with myosin light chain, Mlclp, to effect cytokinesis. Mol Microbiol 53 687-696... 

NO released by GTN activates soluble, cytosolic form of guanylyl cyclase in vascular smooth muscles by interacting with haem group in the enzyme. This converts GTP to cGMP. cGMP dephosphorylates myosin light chain kinase and prevent myosin interaction with actin leading to relaxation. 

Okagaki, T. Ye, L.H. Samizo, K. Tanaka, T. Kohama, K. Inhibitory effect of the catalytic domain of myosin light chain kinase on actin-myosin interaction insight into the mode of inhibition. J. Biochem., 125, 1055-1060 (1999)... 

Vascular tone is regulated by the cytosolic calcium level, the interaction of calcium and calmodulin with myosin light-chain kinase, and subsequent myosin light-chain phosphorylation, which promotes the interaction of myosin with actin and finally leads to contraction. 

An enhancement of ATPase action comes through the phosphorylation of myosin light chains (MW 18,000). The phosphorylation is achieved because the high cellular [Ca2+] activates myosin kinase, an enzyme that contains calmodulin, a Ca2+-binding subunit. Phosphorylation of myosin is absolutely required for smooth muscle contraction, though not for the contraction of skeletal or cardiac muscle, because smooth muscle has no troponin. Thus, whereas contraction and relaxation in skeletal and cardiac muscle are achieved principally via the action of Ca2+ on troponin, in smooth muscle they must depend solely on the Ca2+-dependent phosphorylation of myosin. In skeletal and cardiac muscle, once the stimulus to the sarcolemma is removed, [Ca2+] in sarcoplasm drops rapidly back to 10 7 or 10 8 M via various Ca2+ pump mechanisms present in the sarcoplasmic reticulum, and tropomyosin can once again interfere with the myosin-actin interaction. 

Relaxation follows the drop in cytosolic calcium below the activation threshold, which initiates release of calcium from calmodulin, whereupon calmodulin dissociates from the kinase catalytic subunit. This results in loss of myosin light chain kinase activity. Under these conditions, the dephosphorylation of myosin light chains will be the predominant reaction. Consequently, actin and myosin will no longer interact and the muscle relaxes. 

An increase in Ca2+ (e.g., from 10 8M to 10 5M) acts as the trigger. In striated muscle, Ca2+ is released from the endoplasmic reticulum into the cytoplasm following stimulation of the muscle cell via its attached motor nerve. The Ca2+ interacts with the troponin complex, causing a movement of tropomyosin to expose the myosin binding sites on the thin filaments (see Example 5.21). In smooth muscle, the released Ca2+ indirectly activates myosin light chain kinase which phosphorylates the light chains of myosin. Hence, the control is at the level of the thick filament. In some nonmuscle cells, the control by Ca2+ is at the level of the assembly of myosin into filaments. 

The effects of RhoA activity on spine number and morphology are mediated, at least in part, by the RhoA effector, Rho kinase (Nakayama et al., 2000 Tashiro and Yuste, 2004 Yuste and Bonhoeffer, 2004). Different targets of Rho-kinase have been identified, such as LIMK, myosin light chain (MLC), and MLC phosphatase. Rho-kinase phosphorylates and activates LIMK, which in turn phosphorylates and inactivates the actin depolymerization factor (ADF) cofilin (Maekawa et al., 1999 Sumi et al., 1999 Ohashi et al., 2000 Amano et al., 2001). Phosphorylation of MLC by Rho-kinase results in the stimulation of myosin-actin interactions (Amano et al.,... 

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