title: Novel contributions of the smoothelin-like 1 protein in vascular smooth muscle contraction and its potential involvement in myogenic tone.
abstract: Vascular smooth muscle contraction and the myogenic response regulate blood flow in the resistance vascular and contribute to systemic blood pressure. Three pathways are currently known to contribute to the development of the myogenic response: (i) Ca(2+) -dependent phosphorylation of LC20; (ii) Ca(2+) sensitization through inhibition of myosin phosphatase; and (iii) cortical actin polymerization. A number of regulatory smooth muscle proteins are integrated with these pathways to fine tune the response and facilitate adaptations to vascular (patho)physiologies. Of particular interest is the SMTN family of proteins, consisting of SMTN-A, SMTN-B, and the SMTN-like protein, SMTNL1. The SMTN-B and SMTNL1 proteins are both implicated in regulating smooth muscle contractility and contributing to vascular adaptations associated with hypertension, pregnancy, and exercise training. In the case of SMTNL1, the protein plays multiple roles in regulating contraction through functional interactions with contractile regulators as well as transcriptional control of the contractile phenotype and Ca(2+) -sensitizing capacity. For the first time, preliminary results suggest SMTNL1 is involved in the myogenic response of the cerebral resistance vasculature. In this regard, global SMTNL1 deletion is associated with greater myogenic reactivity of cerebral arterioles, although the precise mechanism accounting for this finding remains to be defined.
authors.affiliation: The Smooth Muscle Research Group at the Libin Cardiovascular Institute of Alberta, Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Turner
authors.forename: Justin A
authors.initials: JA
authors.lastname: MacDonald
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000502:physiology; D001921:Brain / Q000098:blood supply; D020013:Calcium Signaling; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058105:Polymerization; D011247:Pregnancy; D014661:Vasoconstriction / Q000502:physiology; D000096985:Calponins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D043263:Myosin-Light-Chain Phosphatase; D010750:Phosphoproteins; C491520:Ppp1r14a protein, mouse; C543629:SMTNL1 protein, human; D000096985:Calponins; C491838:SMTNL1 protein, mouse
keywords: CHASM; MYPT1; SMTN; SMTNL1; calcium sensitization; cerebral; myosin phosphatase; smoothelin