Layers of smooth muscle cells can be found in the walls of numerous organs and tissues within the body. Smooth muscle tissue lacks the striated banding pattern characteristic of skeletal and cardiac muscle. Smooth muscle is triggered to contract by the autonomic nervous system, hormones, autocrine/paracrine agents, local chemical signals, and changes in load or length.
Actin:myosin cross bridging is used to develop force with the influx of calcium ions (Ca2+) initiating contraction. Two separate protein pathways, both triggered by calcium influx contribute to contraction, a calmodulin driven kinase pathway, and a caldesmon driven pathway.
Recent evidence suggests that actin, myosin, and intermediate filaments may be far more volatile then previously suspected, and that changes in these cytoskeletal elements along with alterations of the focal adhesions that anchor these proteins may contribute to the contractile cycle.
Contraction in smooth muscle generally uses a variant of the same sliding filament model found in striated muscle, except in smooth muscle the actin and myosin filaments are anchored to focal adhesions, and dense bodies, spread over the surface of the smooth muscle cell. When actin and myosin move across one another focal adhesions are drawn towards dense bodies, effectively squeezing the cell into a smaller conformation. The sliding is triggered by calcium:caldesmon binding, caldesmon acting in an analogous fashion to troponin in striated muscle. Phosphorylation of myosin light chains also is involved in the initiation of an effective contraction.
Kumar CC, Mohan SR, Zavodny PJ, Narula SK, Leibowitz PJ.; ''Characterization and differential expression of human vascular smooth muscle myosin light chain 2 isoform in nonmuscle cells.''; PubMedEurope PMCScholia
Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH.; ''The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle.''; PubMedEurope PMCScholia
Cavaillé F, Janmot C, Ropert S, d'Albis A.; ''Isoforms of myosin and actin in human, monkey and rat myometrium. Comparison of pregnant and non-pregnant uterus proteins.''; PubMedEurope PMCScholia
Hathaway DR, Adelstein RS.; ''Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity.''; PubMedEurope PMCScholia
Roostalu U, Strähle U.; ''In vivo imaging of molecular interactions at damaged sarcolemma.''; PubMedEurope PMCScholia
Cai C, Weisleder N, Ko JK, Komazaki S, Sunada Y, Nishi M, Takeshima H, Ma J.; ''Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin.''; PubMedEurope PMCScholia
Morgan KG, Gangopadhyay SS.; ''Invited review: cross-bridge regulation by thin filament-associated proteins.''; PubMedEurope PMCScholia
Mohammad MA, Sparrow MP.; ''The distribution of heavy-chain isoforms of myosin in airways smooth muscle from adult and neonate humans.''; PubMedEurope PMCScholia
Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMedEurope PMCScholia
Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH.; ''Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing.''; PubMedEurope PMCScholia
Once ATP is bound, myosin, which is an ATPase, uses the energy from the cleavage of the terminal phosphate to pivot the myosin head back, away from the actin filamentous chain. This change in conformation "resets" the myosin molecule, leaving it ready to bind the actin filament once more and slide the myosin filament along the actin filament, continuing the contractile cycle.
Caldesmon functions in an analogous fashion to troponin in striated muscle. Once calcium has entered the smooth muscle cell, calcium levels slowly rise. Caldesmon binds calcium, freeing tropomyosin, allowing the tropomyosin to move exposing the active sites on actin for myosin binding.
As soon as the actin and myosin filaments become competent for contraction, the swiveling head of myosin pulls itself along the actin filament. This movement changes the shape of the pocket to which ADP is bound, freeing the ADP molecule.
Once calcium influx occurs, calmodulin is activated by the binding of calcium. The active calmodulin complex binds and activates the smooth muscle myosin light chain kinase (Hathaway and Adelstein 1979, Webb 2003).
The smooth muscle light chain kinase phosphorylates the smooth muscle light chains. This phosphorylation activates the myosin lights chains, effectively allowing contraction to begin.
Mechanical stress and repetitive muscle contraction often causes membrane disruption to the sarcolemma. Healthy muscle is able to repair these disruptions by a Ca2+-dependent pathway. The combination of dysferlin (DYSF), caveolin 3 (CAV3) and tripartite motif-containing protein 72 (TRIM72 aka MG53) appears to be essential for the repair of muscle membrane damage (Cai et al. 2009). DYSF subsequently binds annexin A6 (ANXA6), a member of a family of phospholipid-binding proteins in a Ca2+-dependent manner. This interaction has been demonstrated in imaging experiments in zebrafish (Roostalu U & Strahle 2012). This interaction creates a platform for interacting proteins at the sarcolemma membrane surface and sequential recruitment of annexin A1 and A2 (ANXA1 and 2) to the repair site. The human event is deduced on the basis of experiments performed in mice (Lennon et al. 2003).
Mechanical stress and repetitive muscle contraction often causes membrane disruption to the sarcolemma. Healthy muscle is able to repair these disruptions by a Ca2+-dependent pathway. The combination of dysferlin (DYSF), caveolin 3 (CAV3) and tripartite motif-containing protein 72 TRIM72 aka MG53) appears to be essential for the repair of muscle membrane damage (Cai et al. 2009). CAV3 probably acts as a scaffolding protein in caveolar membranes and can interact with DYSF (Matsuda et al. 2001), a surface membrane protein which promotes the fusion of intracellular vesicles with each other and with the sarcolemma at the site of injury. TRIM72 is required for transport of DYSF to the site of injury.
Try the New WikiPathways
View approved pathways at the new wikipathways.org.Quality Tags
Ontology Terms
Bibliography
History
External references
DataNodes
Myosin Actin
ComplexMuscle Myosin
ComplexMyosin Actin
ComplexActin Contractile
ComplexSmooth Muscle
Myosin Light ChainAnnotated Interactions
Myosin Actin
ComplexMyosin Actin
ComplexMuscle Myosin
ComplexMyosin Actin
ComplexMyosin Actin
ComplexActin Contractile
ComplexSmooth Muscle
Myosin Light Chain