Related Experiment Video
Updated: May 28, 2026
08:57
Myosin-Specific Adaptations of In vitro Fluorescence Microscopy-Based Motility Assays
Published on: February 4, 2021
Vascular smooth muscle myosin light chain diphosphorylation: mechanism, function, and pathological implications.
1Smooth Muscle Research Group and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada. walsh@ucalgary.ca
IUBMB Life
|October 13, 2011
Summary
Smooth muscle contraction involves myosin light chain phosphorylation. Diphosphorylation at S19 and T18 by kinases like ROCK and ZIPK enhances muscle force, offering therapeutic targets for diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Smooth muscle contraction is primarily regulated by the phosphorylation of myosin II regulatory light chain (LC(20)) at serine 19 (S19).
- Alternative phosphorylation sites, such as threonine 18 (T18), can be targeted by various kinases, including integrin-linked kinase (ILK), Rho-associated kinase (ROCK), and zipper-interacting protein kinase (ZIPK).
- These phosphorylation events are conserved across the animal kingdom, indicating fundamental roles in muscle function.
Purpose of the Study:
- To investigate the role of LC(20) diphosphorylation at S19 and T18 in smooth muscle contraction.
- To explore the implications of these phosphorylation events in both physiological and pathophysiological conditions.
- To identify potential therapeutic targets based on the kinases involved in LC(20) phosphorylation.
Main Methods:
- Analysis of myosin II regulatory light chain (LC(20)) phosphorylation sites (S19 and T18).
- Enzymatic assays to determine the effect of phosphorylation on actin-activated myosin MgATPase activity.
- Detection of LC(20) diphosphorylation in mammalian vascular smooth muscle tissues and cultured cells.
- Review of conserved phosphorylation sites in related organisms.
Main Results:
- Kinases like ILK, ROCK, and ZIPK can phosphorylate LC(20) at both S19 and T18.
- Diphosphorylation significantly increases actin-activated myosin MgATPase activity, particularly at low actin concentrations.
- LC(20) diphosphorylation is observed in mammalian vascular smooth muscle under contractile stimuli and in hypercontractile states.
- Diphosphorylation is frequently detected in cultured cells, correlating with increased force generation.
Conclusions:
- LC(20) diphosphorylation at S19 and T18 is a key mechanism for enhancing smooth muscle contractility.
- Kinases such as ILK, ROCK, and ZIPK are crucial regulators of this process.
- Targeting these kinases presents a promising therapeutic strategy for conditions involving smooth muscle hypercontractility, such as cerebral vasospasm and atherosclerosis.
Related Concept Videos
01:15Overview of Myosin Structure and Function
Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X) have been well characterized.
01:25Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
01:18Role of Myosin in Cell Migration
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
01:23Functions of Smooth Muscles
Smooth muscles are an important type of muscle tissue that plays a vital role in the involuntary movements of internal organs. For example, they help regulate the movement of food through the gut and the flow of blood through the circulatory system.
Function of visceral smooth muscles
Visceral smooth muscle is found in the walls of all hollow organs, except the heart, and is a key player in the involuntary movements that drive the functioning of these internal organs. This tissue is arranged in...
Function of visceral smooth muscles
Visceral smooth muscle is found in the walls of all hollow organs, except the heart, and is a key player in the involuntary movements that drive the functioning of these internal organs. This tissue is arranged in...
01:10The Role of Actin and Myosin in Non-muscle Cells
Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They are held...
01:16Actin and Myosin in Muscle Contraction
Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...