Smooth Muscle Contraction (Homo sapiens)

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28, 117, 103, 7, 101, 4, 1312, 132, 67, 103, 7, 10cytoplasmic vesicle lumencytosolTLN1 p-T19,S20-MYL12B MYLK(1-1914)CALM1 TPM3 ATP Bound SmoothMuscle MyosinComplexPXN VCL LMOD1 CAV3:TRIM72:DYSFp-S23-MYL7 DYSF SORBS1 p-S19-MYL12A p-S23-MYL7 DYSFPhosphorylatedSmooth MuscleMyosin Light Chainp-S20-MYL9 p-S20-MYL6B TPM2 p-S20-MYL6 MYLPF SORBS1 ATP ITGB5 ADP:Calcium BoundMyosin ActinComplexp-S21-MYL5 p-S20-MYL9 p-T19,S20-MYL12B p-S20-MYL6B Ca2+ACTA2 p-S20-MYL6B PXN SORBS1 PXN p-S,T-MYL10 ANXA6 p-S,T-MYL10 MYL6B p-S16-MYLPF p-T19,S20-MYL12B TLN1 ACTA2 p-S,T-PAK1,2TPM3 p-S20-MYL9 MYL12B Calcium Bound MyosinActin ComplexTPM1 ACTA2 p-S16-MYLPF p-S20-MYL6 ATPp-S19-MYL12A p-S16-MYLPF p-S19-MYL12A ADPp-S19-MYL12A p-T19,S20-MYL12B VCL PiInactive MyosinActin ContractileComplexTPM4 ANXA6ANXA1TLN1 TPM2 ANXA2 MYL6 p-S20-MYL6B DYSF ADPCALM1 p-S21-MYL5 TLN1 Ca2+ MYH11 ANXA1 SORBS3 LMOD1 MYLK(1-1914) p-S21-MYL5 ANXA2TPM4 TRIM72p-S23-MYL7 p-S20-MYL6 TPM1 SORBS3 p-S19-MYL12A MYH11 ITGA1 MYL7 TRIM72 p-S23-MYL7 MYL9 p-S16-MYLPF TPM2 ADP ITGB5 ACTG2 TPM1 ACTA2 SORBS3 p-S,T-MYL10 ATP:Calcium BoundMyosin ActinComplexp-S,T-MYL10 MYL10 TPM2 VCL MYH11 p-S23-MYL7 p-S16-MYLPF MYH11 p-S141,T402-PAK2 CAV3PXN MYLK:Ca2+:CALM1p-S21-MYL5 p-S20-MYL6 CAV3 ITGA1 TPM3 CALM1CALD1 SORBS3 p-T19,S20-MYL12B p-S,T-MYL10 CAV3:TRIM72:DYSF:ANXA6:ANXA1:ANXA2Ca2+p-S21-MYL5 p-T19,S20-MYL12B VCL SORBS1 ITGA1 p-S20-MYL6 ATP p-S20-MYL6 p-S144,T423-PAK1 p-S,T-MYL10 TPM3 Ca2+ Ca2+ TPM4 TRIM72 p-S19-MYL12A p-S20-MYL9 CAV3 ITGB5 ACTG2 LMOD1 CALM1:4xCa2+p-S23-MYL7 ITGB5 MYL5 CALD1 ACTG2 MYH11 p-S20-MYL6B p-S20-MYL6B ACTG2 ITGA1 Ca2+ Smooth Muscle MyosinLight ChainLMOD1 Ca2+ TPM1 TPM4 CALD1 p-S21-MYL5 p-S20-MYL9 CALD1 ATPp-S20-MYL9 p-S16-MYLPF MYL12A 95


Description

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.

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Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 445355
Reactome-version 
Reactome version: 63
Reactome Author 
Reactome Author: Gillespie, Marc E

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Bibliography

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  1. Qualmann B, Kessels MM.; ''New players in actin polymerization--WH2-domain-containing actin nucleators.''; PubMed Europe PMC Scholia
  2. 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.''; PubMed Europe PMC Scholia
  3. 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.''; PubMed Europe PMC Scholia
  4. 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.''; PubMed Europe PMC Scholia
  5. Hathaway DR, Adelstein RS.; ''Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity.''; PubMed Europe PMC Scholia
  6. Roostalu U, Strähle U.; ''In vivo imaging of molecular interactions at damaged sarcolemma.''; PubMed Europe PMC Scholia
  7. 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.''; PubMed Europe PMC Scholia
  8. Morgan KG, Gangopadhyay SS.; ''Invited review: cross-bridge regulation by thin filament-associated proteins.''; PubMed Europe PMC Scholia
  9. Webb RC.; ''Smooth muscle contraction and relaxation.''; PubMed Europe PMC Scholia
  10. Mohammad MA, Sparrow MP.; ''The distribution of heavy-chain isoforms of myosin in airways smooth muscle from adult and neonate humans.''; PubMed Europe PMC Scholia
  11. 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.''; PubMed Europe PMC Scholia
  12. Marston SB, Redwood CS.; ''The molecular anatomy of caldesmon.''; PubMed Europe PMC Scholia
  13. Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH.; ''Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115052view16:59, 25 January 2021ReactomeTeamReactome version 75
113496view11:57, 2 November 2020ReactomeTeamReactome version 74
112696view16:09, 9 October 2020ReactomeTeamReactome version 73
101613view11:48, 1 November 2018ReactomeTeamreactome version 66
101149view21:34, 31 October 2018ReactomeTeamreactome version 65
100677view20:07, 31 October 2018ReactomeTeamreactome version 64
100227view16:52, 31 October 2018ReactomeTeamreactome version 63
99778view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93385view11:22, 9 August 2017ReactomeTeamreactome version 61
86471view09:19, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACTA2 ProteinP62736 (Uniprot-TrEMBL)
ACTG2 ProteinP63267 (Uniprot-TrEMBL)
ADP MetaboliteCHEBI:16761 (ChEBI)
ADP:Calcium Bound

Myosin Actin

Complex
ComplexR-HSA-445697 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ANXA1 ProteinP04083 (Uniprot-TrEMBL)
ANXA1ProteinP04083 (Uniprot-TrEMBL)
ANXA2 ProteinP07355 (Uniprot-TrEMBL)
ANXA2ProteinP07355 (Uniprot-TrEMBL)
ANXA6 ProteinP08133 (Uniprot-TrEMBL)
ANXA6ProteinP08133 (Uniprot-TrEMBL)
ATP Bound Smooth

Muscle Myosin

Complex
ComplexR-HSA-445789 (Reactome)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATP:Calcium Bound

Myosin Actin

Complex
ComplexR-HSA-445701 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
CALD1 ProteinQ05682 (Uniprot-TrEMBL)
CALM1 ProteinP0DP23 (Uniprot-TrEMBL)
CALM1:4xCa2+ComplexR-HSA-74294 (Reactome)
CALM1ProteinP0DP23 (Uniprot-TrEMBL)
CAV3 ProteinP56539 (Uniprot-TrEMBL)
CAV3:TRIM72:DYSF:ANXA6:ANXA1:ANXA2ComplexR-HSA-5263623 (Reactome)
CAV3:TRIM72:DYSFComplexR-HSA-5263629 (Reactome)
CAV3ProteinP56539 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcium Bound Myosin Actin ComplexComplexR-HSA-445702 (Reactome)
DYSF ProteinO75923 (Uniprot-TrEMBL)
DYSFProteinO75923 (Uniprot-TrEMBL)
ITGA1 ProteinP56199 (Uniprot-TrEMBL)
ITGB5 ProteinP18084 (Uniprot-TrEMBL)
Inactive Myosin

Actin Contractile

Complex
ComplexR-HSA-445703 (Reactome)
LMOD1 ProteinP29536 (Uniprot-TrEMBL)
MYH11 ProteinP35749 (Uniprot-TrEMBL)
MYL10 ProteinQ9BUA6 (Uniprot-TrEMBL)
MYL12A ProteinP19105 (Uniprot-TrEMBL)
MYL12B ProteinO14950 (Uniprot-TrEMBL)
MYL5 ProteinQ02045 (Uniprot-TrEMBL)
MYL6 ProteinP60660 (Uniprot-TrEMBL)
MYL6B ProteinP14649 (Uniprot-TrEMBL)
MYL7 ProteinQ01449 (Uniprot-TrEMBL)
MYL9 ProteinP24844 (Uniprot-TrEMBL)
MYLK(1-1914) ProteinQ15746 (Uniprot-TrEMBL)
MYLK(1-1914)ProteinQ15746 (Uniprot-TrEMBL)
MYLK:Ca2+:CALM1ComplexR-HSA-445764 (Reactome)
MYLPF ProteinQ96A32 (Uniprot-TrEMBL)
PXN ProteinP49023 (Uniprot-TrEMBL)
Phosphorylated

Smooth Muscle

Myosin Light Chain
ComplexR-HSA-445770 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
SORBS1 ProteinQ9BX66 (Uniprot-TrEMBL)
SORBS3 ProteinO60504 (Uniprot-TrEMBL)
Smooth Muscle Myosin Light ChainComplexR-HSA-445793 (Reactome)
TLN1 ProteinQ9Y490 (Uniprot-TrEMBL)
TPM1 ProteinP09493 (Uniprot-TrEMBL)
TPM2 ProteinP07951 (Uniprot-TrEMBL)
TPM3 ProteinP06753 (Uniprot-TrEMBL)
TPM4 ProteinP67936 (Uniprot-TrEMBL)
TRIM72 ProteinQ6ZMU5 (Uniprot-TrEMBL)
TRIM72ProteinQ6ZMU5 (Uniprot-TrEMBL)
VCL ProteinP18206 (Uniprot-TrEMBL)
p-S,T-MYL10 ProteinQ9BUA6 (Uniprot-TrEMBL)
p-S,T-PAK1,2ComplexR-HSA-5668976 (Reactome)
p-S141,T402-PAK2 ProteinQ13177 (Uniprot-TrEMBL)
p-S144,T423-PAK1 ProteinQ13153 (Uniprot-TrEMBL)
p-S16-MYLPF ProteinQ96A32 (Uniprot-TrEMBL)
p-S19-MYL12A ProteinP19105 (Uniprot-TrEMBL)
p-S20-MYL6 ProteinP60660 (Uniprot-TrEMBL)
p-S20-MYL6B ProteinP14649 (Uniprot-TrEMBL)
p-S20-MYL9 ProteinP24844 (Uniprot-TrEMBL)
p-S21-MYL5 ProteinQ02045 (Uniprot-TrEMBL)
p-S23-MYL7 ProteinQ01449 (Uniprot-TrEMBL)
p-T19,S20-MYL12B ProteinO14950 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADP:Calcium Bound

Myosin Actin

Complex
ArrowR-HSA-445699 (Reactome)
ADP:Calcium Bound

Myosin Actin

Complex
R-HSA-445705 (Reactome)
ADPArrowR-HSA-445705 (Reactome)
ADPArrowR-HSA-445813 (Reactome)
ANXA1R-HSA-5263628 (Reactome)
ANXA2R-HSA-5263628 (Reactome)
ANXA6R-HSA-5263628 (Reactome)
ATP Bound Smooth

Muscle Myosin

Complex
mim-catalysisR-HSA-445699 (Reactome)
ATP:Calcium Bound

Myosin Actin

Complex
ArrowR-HSA-445700 (Reactome)
ATP:Calcium Bound

Myosin Actin

Complex
R-HSA-445699 (Reactome)
ATPR-HSA-445700 (Reactome)
ATPR-HSA-445813 (Reactome)
CALM1:4xCa2+ArrowR-HSA-74448 (Reactome)
CALM1:4xCa2+R-HSA-445797 (Reactome)
CALM1R-HSA-74448 (Reactome)
CAV3:TRIM72:DYSF:ANXA6:ANXA1:ANXA2ArrowR-HSA-5263628 (Reactome)
CAV3:TRIM72:DYSFArrowR-HSA-5263633 (Reactome)
CAV3:TRIM72:DYSFR-HSA-5263628 (Reactome)
CAV3R-HSA-5263633 (Reactome)
Ca2+ArrowR-HSA-5263628 (Reactome)
Ca2+ArrowR-HSA-5263633 (Reactome)
Ca2+R-HSA-445704 (Reactome)
Ca2+R-HSA-74448 (Reactome)
Calcium Bound Myosin Actin ComplexArrowR-HSA-445704 (Reactome)
Calcium Bound Myosin Actin ComplexArrowR-HSA-445705 (Reactome)
Calcium Bound Myosin Actin ComplexR-HSA-445700 (Reactome)
DYSFR-HSA-5263633 (Reactome)
Inactive Myosin

Actin Contractile

Complex
R-HSA-445704 (Reactome)
MYLK(1-1914)R-HSA-445797 (Reactome)
MYLK:Ca2+:CALM1ArrowR-HSA-445797 (Reactome)
MYLK:Ca2+:CALM1mim-catalysisR-HSA-445813 (Reactome)
Phosphorylated

Smooth Muscle

Myosin Light Chain
ArrowR-HSA-445813 (Reactome)
PiArrowR-HSA-445699 (Reactome)
R-HSA-445699 (Reactome) 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.
R-HSA-445700 (Reactome) With the expulsion of ADP from the nucleotide binding pocket, ATP, if available will immediately bind.
R-HSA-445704 (Reactome) 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.
R-HSA-445705 (Reactome) 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.
R-HSA-445797 (Reactome) 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).
R-HSA-445813 (Reactome) The smooth muscle light chain kinase phosphorylates the smooth muscle light chains. This phosphorylation activates the myosin lights chains, effectively allowing contraction to begin.
R-HSA-5263628 (Reactome) 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).
R-HSA-5263633 (Reactome) 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.
R-HSA-74448 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
Smooth Muscle Myosin Light ChainR-HSA-445813 (Reactome)
TRIM72R-HSA-5263633 (Reactome)
p-S,T-PAK1,2TBarR-HSA-445797 (Reactome)
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