Limits...
Smooth muscle signalling pathways in health and disease.

Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG - J. Cell. Mol. Med. (2008)

Bottom Line: Smooth muscle contractile activity is a major regulator of function of the vascular system, respiratory system, gastrointestinal system and the genitourinary systems.Malfunction of contractility in these systems leads to a host of clinical disorders, and yet, we still have major gaps in our understanding of the molecular mechanisms by which contractility of the differentiated smooth muscle cell is regulated.This review will summarize recent advances in the molecular understanding of the regulation of smooth muscle myosin activity via phosphorylation/dephosphorylation of myosin, the regulation of the accessibility of actin to myosin via the actin-binding proteins calponin and caldesmon, and the remodelling of the actin cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, Boston University, Boston, MA 02215, USA.

ABSTRACT
Smooth muscle contractile activity is a major regulator of function of the vascular system, respiratory system, gastrointestinal system and the genitourinary systems. Malfunction of contractility in these systems leads to a host of clinical disorders, and yet, we still have major gaps in our understanding of the molecular mechanisms by which contractility of the differentiated smooth muscle cell is regulated. This review will summarize recent advances in the molecular understanding of the regulation of smooth muscle myosin activity via phosphorylation/dephosphorylation of myosin, the regulation of the accessibility of actin to myosin via the actin-binding proteins calponin and caldesmon, and the remodelling of the actin cytoskeleton. Understanding of the molecular 'players' should identify target molecules that could point the way to novel drug discovery programs for the treatment of smooth muscle disorders such as cardiovascular disease, asthma, functional bowel disease and pre-term labour.

Show MeSH

Related in: MedlinePlus

Cytoskeletal remodelling at focal adhesions and regulation of smooth muscle contraction. Integrins connect the extracellular matrix to actin filaments within the cell. Actin filaments are linked to cytoplasmic domain of integrin by linker proteins (green). Mechanical and/or contractile stimuli induce the cytoskeletal remodelling by recruiting signalling proteins (orange) to focal adhesions.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2692531&req=5

fig06: Cytoskeletal remodelling at focal adhesions and regulation of smooth muscle contraction. Integrins connect the extracellular matrix to actin filaments within the cell. Actin filaments are linked to cytoplasmic domain of integrin by linker proteins (green). Mechanical and/or contractile stimuli induce the cytoskeletal remodelling by recruiting signalling proteins (orange) to focal adhesions.

Mentions: Actin can exist as either filamentous actin (F-actin) or globular actin (G-actin) in cells. G-actin spontaneously polymerizes to form F-actin above its critical concentration (∼8 μg/ml) [165]. The G-actin concentration in the cytoplasm of dVSM cells is above the critical concentration. However, the polymerization of actin is tightly controlled by a large number of actin-binding proteins such as profilin, ADF/cofilin, capping proteins, and sequestering proteins, etc. Signalling pathways that regulate these processes therefore regulate the actual ratio between G- and F-actin resulting in assembly or disassembly of the actin filament (Fig.6) [165,166].


Smooth muscle signalling pathways in health and disease.

Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG - J. Cell. Mol. Med. (2008)

Cytoskeletal remodelling at focal adhesions and regulation of smooth muscle contraction. Integrins connect the extracellular matrix to actin filaments within the cell. Actin filaments are linked to cytoplasmic domain of integrin by linker proteins (green). Mechanical and/or contractile stimuli induce the cytoskeletal remodelling by recruiting signalling proteins (orange) to focal adhesions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2692531&req=5

fig06: Cytoskeletal remodelling at focal adhesions and regulation of smooth muscle contraction. Integrins connect the extracellular matrix to actin filaments within the cell. Actin filaments are linked to cytoplasmic domain of integrin by linker proteins (green). Mechanical and/or contractile stimuli induce the cytoskeletal remodelling by recruiting signalling proteins (orange) to focal adhesions.
Mentions: Actin can exist as either filamentous actin (F-actin) or globular actin (G-actin) in cells. G-actin spontaneously polymerizes to form F-actin above its critical concentration (∼8 μg/ml) [165]. The G-actin concentration in the cytoplasm of dVSM cells is above the critical concentration. However, the polymerization of actin is tightly controlled by a large number of actin-binding proteins such as profilin, ADF/cofilin, capping proteins, and sequestering proteins, etc. Signalling pathways that regulate these processes therefore regulate the actual ratio between G- and F-actin resulting in assembly or disassembly of the actin filament (Fig.6) [165,166].

Bottom Line: Smooth muscle contractile activity is a major regulator of function of the vascular system, respiratory system, gastrointestinal system and the genitourinary systems.Malfunction of contractility in these systems leads to a host of clinical disorders, and yet, we still have major gaps in our understanding of the molecular mechanisms by which contractility of the differentiated smooth muscle cell is regulated.This review will summarize recent advances in the molecular understanding of the regulation of smooth muscle myosin activity via phosphorylation/dephosphorylation of myosin, the regulation of the accessibility of actin to myosin via the actin-binding proteins calponin and caldesmon, and the remodelling of the actin cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, Boston University, Boston, MA 02215, USA.

ABSTRACT
Smooth muscle contractile activity is a major regulator of function of the vascular system, respiratory system, gastrointestinal system and the genitourinary systems. Malfunction of contractility in these systems leads to a host of clinical disorders, and yet, we still have major gaps in our understanding of the molecular mechanisms by which contractility of the differentiated smooth muscle cell is regulated. This review will summarize recent advances in the molecular understanding of the regulation of smooth muscle myosin activity via phosphorylation/dephosphorylation of myosin, the regulation of the accessibility of actin to myosin via the actin-binding proteins calponin and caldesmon, and the remodelling of the actin cytoskeleton. Understanding of the molecular 'players' should identify target molecules that could point the way to novel drug discovery programs for the treatment of smooth muscle disorders such as cardiovascular disease, asthma, functional bowel disease and pre-term labour.

Show MeSH
Related in: MedlinePlus