Actin polymerization stimulated by contractile activation regulates force development in canine tracheal smooth muscle

Mehta, Dolly; Gunst, Susan J.

doi:10.1111/j.1469-7793.1999.0829n.x

Cited by 224 publications

(329 citation statements)

References 51 publications

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“…In colonic smooth muscle cells, Hsp27 binds to and modulates the interactions of myosin, tropomyosin, and caldesmon (5,47). However, Hsp27 also binds to actin filaments, and the remodeling of the latter may be associated with smooth muscle contractility (4,11,33). Reorganization of the actin cytoskeleton is known to occur during smooth muscle contraction (17), and we have previously shown that NE activates p38 MAPK/Hsp27 kinase in RMSAs (36) and that the inhibition of this pathway or disruption of the cytoskeleton blocks contraction (38).…”

Section: Discussionmentioning

confidence: 99%

“…Given the importance of ␣-adrenergic signaling in the regulation of small artery contractility and evidence that during agonist-stimulated contraction of smooth muscle tissue actin polymerization occurs and is necessary for force development (4,11,33), we investigated the activation of Hsp27 and Hic-5 and studied their interaction in rat mesenteric small arteries (RMSAs) after NE stimulation.…”

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confidence: 99%

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Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Srinivasan¹,

Forman²,

Quinlan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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regulation of small artery contractility by vasoconstrictors is important for vascular function, and actin cytoskeleton remodeling is required for contraction. p38 MAPK and tyrosine kinases are implicated in actin polymerization and contraction through heat shock protein 27 (Hsp27) and the cytoskeletal protein paxillin, respectively. We evaluated the roles of downstream targets of p38 MAPK and tyrosine kinases in cytoskeletal reorganization and contraction and whether the two signaling pathways regulate contraction independent of each other. We identified the expression of the paxillin homologue hydrogen peroxide-inducible clone-5 (Hic-5) and showed its activation by norepinephrine (NE) in a Src-dependent manner. Furthermore, we demonstrated a NE-induced interaction of proline-rich tyrosine kinase-2 (PYK2) but not Src or p125 focal adhesion kinase with Hic-5. This interaction was Src dependent, suggesting that Hic-5 was a substrate for PYK2 downstream from Src. The activation of Hic-5 induced its relocalization to the cytosol. The parallel activation of Hsp27 by NE was p38 MAPK dependent and led to its dissociation from actin filaments and translocation from membrane to cytosol and increased actin polymerization. Both Hsp27 and Hic-5 activation resulted in their association within the same time frame as NEinduced contraction, and the inhibition of either p38 MAPK or Src inhibited the interaction between Hsp27 and Hic-5 and the contractile response. Furthermore, combined p38 MAPK and Src inhibition had no greater effect on contraction than individual inhibition, suggesting that the two pathways act through a common mechanism. These data show that NE-induced activation and the association of Hsp27 and Hic-5 are required for the reorganization of the actin cytoskeleton and force development in small arteries.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Srinivasan¹,

Forman²,

Quinlan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Studies performed primarily in tracheal smooth muscle indicate that remodeling of the actin cytoskeleton is required for the full development of force induced by stimulation with contractile agonists (94,113,183). The process involves increased polymerization of actin, tyrosine phosphorylation of paxillin, the activation of the small GTP-binding proteins Rho and Cdc42, and conformational changes within focal adhesion sites involving specific focal adhesion proteins (161,164,180,181).…”

Section: Reviewsmentioning

confidence: 99%

The Plastic Nature of the Vascular Wall: A Continuum of Remodeling Events Contributing to Control of Arteriolar Diameter and Structure

2009

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The diameter of resistance arteries has a profound effect on the distribution of microvascular blood flow and the control of systemic blood pressure. Here, we review mechanisms that contribute to the regulation of resistance artery diameter, both acutely and chronically, their temporal characteristics, and their interdependence. Furthermore, we hypothesize the existence of a remodeling continuum that allows for the vascular wall to rapidly modify its structural characteristics, specifically through the re-positioning of vascular smooth muscle cells.Importantly, the concepts presented more closely link acute vasoregulatory responses with adaptive changes in vessel wall structure. These rapid structural adaptations provide resistance vessels the ability to maintain a desired diameter under presumed optimal energetic and mechanical conditions.1548-9213/09 8.00

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“…Contractile agonists have been shown to stimulate actin polymerization in a number of smooth muscle cells and tissues, and the critical role of actin polymerization in regulating active tension development in smooth muscle is well documented (4,8,12,16,18,22,29,38,63,64,67). The inhibition of actin polymerization using either pharmacologic or molecular approaches has been shown to depress tension development in many smooth muscles with little or no effect on MLC phosphorylation or cross-bridge cycling (16, 38, 42, 43, 49, 51, 57-59, 64, 65).…”

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confidence: 99%

The effects of the small GTPase RhoA on the muscarinic contraction of airway smooth muscle result from its role in regulating actin polymerization

Zhang

Gunst

2010

American Journal of Physiology-Cell Physiology

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Zhang W, Du L, Gunst SJ. The effects of the small GTPase RhoA on the muscarinic contraction of airway smooth muscle result from its role in regulating actin polymerization. Am J Physiol Cell Physiol 299: C298 -C306, 2010. First published May 5, 2010 doi:10.1152/ajpcell.00118.2010.-The small GTPase RhoA increases the Ca 2ϩ sensitivity of smooth muscle contraction and myosin light chain (MLC) phosphorylation by inhibiting the activity of MLC phosphatase. RhoA is also a known regulator of cytoskeletal dynamics and actin polymerization in many cell types. In airway smooth muscle (ASM), contractile stimulation induces MLC phosphorylation and actin polymerization, which are both required for active tension generation. The objective of this study was to evaluate the primary mechanism by which RhoA regulates active tension generation in intact ASM during stimulation with acetylcholine (ACh). RhoA activity was inhibited in canine tracheal smooth muscle tissues by expressing the inactive RhoA mutant, RhoA T19N, in the intact tissues or by treating them with the cell-permeant RhoA inhibitor, exoenzyme C3 transferase. RhoA inactivation reduced ACh-induced contractile force by ϳ60% and completely inhibited ACh-induced actin polymerization but inhibited ACh-induced MLC phosphorylation by only ϳ20%. Inactivation of MLC phosphatase with calyculin A reversed the reduction in MLC phosphorylation caused by RhoA inactivation, but calyculin A did not reverse the depression of active tension and actin polymerization caused by RhoA inactivation. The MLC kinase inhibitor, ML-7, inhibited ACh-induced MLC phosphorylation by ϳ80% and depressed active force by ϳ70% but did not affect ACh-induced actin polymerization, demonstrating that AChstimulated actin polymerization occurs independently of MLC phosphorylation. We conclude that the RhoA-mediated regulation of ACh-induced contractile tension in ASM results from its role in mediating actin polymerization rather than from effects on MLC phosphatase or MLC phosphorylation. cytoskeleton; calcium sensitization; myosin light chain phosphorylation; myosin light chain phosphatase; myosin phosphatase; calyculin A; myosin light chain kinase

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Actin polymerization stimulated by contractile activation regulates force development in canine tracheal smooth muscle

Cited by 224 publications

References 51 publications

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

The Plastic Nature of the Vascular Wall: A Continuum of Remodeling Events Contributing to Control of Arteriolar Diameter and Structure

The effects of the small GTPase RhoA on the muscarinic contraction of airway smooth muscle result from its role in regulating actin polymerization

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