Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle

Dale D Tang; Yana Anfinogenova

doi:10.1177/1074248407313737

. Author manuscript; available in PMC: 2009 Jun 1.

Published in final edited form as: J Cardiovasc Pharmacol Ther. 2008 Jan 22;13(2):130–140. doi: 10.1177/1074248407313737

Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle

Dale D Tang ¹, Yana Anfinogenova ¹

PMCID: PMC2396785 NIHMSID: NIHMS37967 PMID: 18212360

Abstract

Vascular smooth muscle tone plays a fundamental role in regulating blood pressure, blood flow, microcirculation, and other cardiovascular functions. The cellular and molecular mechanisms by which vascular smooth muscle contractility is regulated are not completely elucidated. Recent studies show that the actin cytoskeleton in smooth muscle is dynamic, which regulates force development. In this review, evidence for actin polymerization in smooth muscle upon external stimulation is summarized. Protein kinases, such as Abl, FAK, Src, and MAP kinase, have been documented to coordinate actin polymerization in smooth muscle. Transmembrane integrins have also been reported to link to signaling pathways modulating actin dynamics. The roles of Rho family of the small GTPases and the actin-regulatory proteins including CAS, N-WASP, the Arp2/3 complex, profilin, and heat shock proteins in regulating actin assembly are discussed. These new findings promote our understanding on how smooth muscle contraction is regulated at cellular and molecular levels.

Keywords: Vascular smooth muscle, actin cytoskeleton, contraction

Introduction

Vascular smooth muscle tone plays a fundamental role in regulating blood pressure, blood flow, microcirculation, and other cardiovascular functions. Abnormal smooth muscle contraction may result in the development of many diseases such as primary hypertension, ischemic heart disease, pulmonary hypertension, and stroke.

Smooth muscles exhibit a unique capability to contract and relax in response to changes in the environment surrounding them. Smooth muscles may adapt their contractile status by remodeling cellular structures and by altering signaling cascades regarding contractile element activation.

The contractile apparatus of smooth muscle is comprised of thin filaments containing actin and thick filaments containing myosin. Actin filaments of smooth muscle cells connect with dense plaques on the membrane, and link to dense bodies in the myoplasm. The majority of actin filaments localize around thick filaments in a hexagonal array, forming the contractile apparatus. This pool of actin filaments is called “contractile actin”. Part of actin filaments is not structurally associated with myosin. It is called “cytoskeletal actin”, which plays a role in maintaining structural integrity of smooth muscle cells (Fig. 1). The detailed structure of smooth muscle cells has previously been reviewed ¹^-³.

**(A & B)** Actin filaments connect with dense plaques (DP) on the membrane (M), and link to dense bodies (DB) in the myoplasm. The majority of actin filaments localize around myosin filaments (My) in a hexagonal array, forming the contractile apparatus. This pool of actin filaments is called “contractile actin (CA)”. Part of actin filaments is not structurally associated with myosin. It is called “cytoskeletal actin (CskA)”. **(C)** Actin polymerization occurs at the barbed end locating near the membrane whereas actin depolymerization takes place at the opposite of the barbed end. At the dense plaque, actin filaments attach to transmembrane integrins via linker proteins such as talin and vinculin.

A wealth of evidence has been documented to suggest that the actin cytoskeleton of smooth muscle undergoes a dynamic remodeling process, which is a key component of the structural adaptation upon changes in chemical and mechanical environments ⁴^,⁵. In this article, we will review our recent understanding on the role and regulation of the actin cytoskeleton system in smooth muscle.

Physiologic properties of the actin cytoskeleton in arterial smooth muscle

Actin filament polymerization occurs in response to contractile and mechanical stimulation

The actin cytoskeleton in differentiated smooth muscle cells and tissues has long been thought to be a fixed structure. Recent studies have documented that the actin architecture of smooth muscle is in a dynamic state; polymerization-depolymerization of actin filaments participates in the contraction-relaxation cycle of smooth muscle. Studies on carotid smooth muscle have shown that the ratio of filamentous (F) actin to globular (G) actin is approximately 1.8 in unstimulated arterial smooth muscle tissues, suggesting that approximately 25-30% of total actin exists in the form of actin monomers ⁶^,⁷. The F-actin/G-actin ratio increases to 5.8 in response to contractile stimulation, indicating that approximately 10-15% of total actin is G-actin. The F-actin/G-actin ratio decreases to basal level during the relaxation process.

The dynamic feature of the actin cytoskeleton has also been observed in other studies; the amount of actin monomers is decreased, or the fraction of filamentous actin is increased during contractile stimulation ⁸^-¹⁶. In cultured airway smooth muscle cells, treatment with carbachol and endothelin-1 leads to the increase in the ratio of F-actin to G-actin as estimated by cytofluorescence analysis, whereas treatment with smooth muscle relaxant (isoproteronol and forskolin) decreases the F-actin/G-actin ratio ¹⁷^,¹⁸. Consistent with these findings, Barany and colleagues ¹⁹ have reported a high concentration of G-actin in vascular smooth muscle tissues by assessing the exchange rates of actin-bound nucleotide, and observed a decrease of the G-actin pool in response to contractile stimulation. These studies demonstrate that actin filament assembly occurs in various smooth muscle cell/tissue types, which may be a unique phenomenon in smooth muscle in response to contractile activation.

Changes in mechanical environments also affect actin filament reorganization. A single stretch imposed on the cell membrane alters the stiffness of the cell, which is intimately associated with the status of the actin cytoskeleton ²⁰^,²¹. Passive tension also induces the tyrosine phosphorylation of the cytoskeletal protein paxillin, an index of the actin cytoskeleton reorganization ⁸^,²²^,²³. Furthermore, mechanical signals locally imposed on cells triggers structural reorganization of the actin architecture in smooth muscle cells ⁴^,⁵^,²⁴.

Actin polymerization is believed to occur at the barbed end of actin filaments, which is located near the membrane of smooth muscle cells. At the barbed end, globular (G) actin is added onto existing filamentous (F) actin. This process is regulated by various actin associated proteins (See below). Actin depolymerization takes place at the point end of actin filaments, which positions the opposite of the barbed end (Fig. 1) ¹^,¹⁰^,¹²^,¹³^,²⁵^-²⁷.

The dynamic feature of actin filaments in smooth muscle is markedly distinctive as compared to striated muscle; a significant G-actin pool is not detected and the rate of actin-bound nucleotide exchange is very low in skeletal muscle¹⁹^,²⁸. Smooth muscle tissues also contain a much higher ratio of F-actin to myosin than skeletal muscle, and in contrast to skeletal muscle, they maintain a significant pool of F-actin that does not interact with myosin ²^,²⁹.

Actin filament assembly participates in contractile force development

There is compelling evidence that the depression of actin polymerization by such inhibitors as cytochalasin or latrunculin attenuates force development in a variety of smooth muscle tissues ⁶^-⁸^,³⁰^-³². The short-term treatment of smooth muscle with these inhibitors does not impair the actin cytoskeleton; no differences in contractile filament organization or ultrastructure are detected in smooth muscle strips treated with cytochalasin or latrunculin as compared to control tissues ⁸. Latrunculin binds to actin monomers and prevents their assembly onto actin filaments whereas cytochalasin caps existing actin filaments, preventing their extension at the barbed end ⁸^,³³^,³⁴. More importantly, the depression of actin polymerization disrupts force development in smooth muscle with little or no effects on myosin phosphorylation, a cellular event that is crucial for smooth muscle contraction ⁶^,⁸^,¹⁰. These studies suggest: 1) new actin polymerization per se is a necessary step in the cellular process for force development; 2) actin filament assembly and myosin phosphorylation are independent cellular events; and 3) both actin filament polymerization and myosin activation are required for smooth muscle contraction.

There are several possibilities that actin polymerization may affect force development. First, the actin filaments of smooth muscle cells connect to the membrane at the membrane-associated dense plaques, which are structurally similar to focal adhesion sites of cultured cells. At these structures, the cytoplasmic domain of β integrins associates with linker proteins such as vinculin and talin that in turn attach to actin filaments. The extracellular portion of β integrins engages with extracellular matrix ¹^,²^,³⁵^,³⁶. Thus, the membrane-associated dense plaques have been believed to mediate mechanical force transmission between actin filaments to extracellular matrix ¹^,⁴^,³⁶. Recent studies have shown that actin polymerization is initiated by the Arp2/3 (Actin Related Protein) complex in non-muscle cells as well as in smooth muscle, indicating that nascent actin polymerization may occur at cell cortex ¹⁰^,¹²^,¹³^,³⁷^,³⁸. Cortical actin assembly may strengthen the linkage of actin filaments to integrins and enhance the transmission of contractile force ¹^,⁴^,⁵^,¹⁰^,¹²^,¹³^,²⁷^,³⁵^,³⁶^,³⁹^-⁴².

Second, actin assembly has been shown to increase the number of contractile units and the length of actin filaments, providing more and efficient contractile elements for force development ³¹^,⁴³^-⁴⁶. Third, newly polymerized filaments may be a part of reorganization processes that allow for rapid adjustment of stiffness and tension ¹^,⁴^,⁵^,¹⁰^,¹²^,¹³^,³⁵^,⁴⁷^-⁵¹. Fourth, actin filament assembly may participate in the “latch” formation of contractile elements, supporting force maintenance under the condition of lower crossbridge phosphorylation ¹⁵^,¹⁶^,³⁵^,⁵²^-⁵⁴.

Cellular processes regulating actin dynamics in smooth muscle

In the last several years, considerable efforts have been made from a number of laboratories to explore how actin filament assembly is regulated in smooth muscle. Thus far protein kinases, such as Abelson tyrosine kinase (Abl), focal adhesion kinase (FAK), Src, mitogen-activated protein (MAP) kinase and other kinases, have been documented to coordinate actin polymerization in smooth muscle. Transmembrane integrins have also been reported to link to signaling pathways modulating the actin cytoskeleton. Rho, Cdc42, and Rac are the major members of Rho family of the small GTPases that mediates actin dynamics in smooth muscle. The actin-regulatory proteins are effector molecules in the signaling cascades to mediate actin dynamics. Some of the proteins are neuronal Wiskott-Aldrich syndrome Protein (N-WASP), the Arp2/3 complex, profilin, cofilin, and heat shock proteins. In general, receptor activation and/or integrin ligation activates protein kinases and/or small GTPases, which in turn regulate the functional status of the actin regulatory proteins and eventually actin filament assembly or structural reorganization (Fig. 2).

Contractile agonists and mechanical signals activate proteins kinases (Abl, FAK, Src, MAP kinase, etc) and small GTPases (Rho, Cdc42 and Rac) that regulate the downstream effectors (CAS/CrkII, N-WASP, the Arp2/3 complex, profilin, paxillin/Hic-5, HSP27, cofilin, etc.), actin polymerization, and cytoskeletal remodeling. Intracellular Ca²⁺ modulated by electrical signals (depolarization), receptor, and FAK/Src may mediate actin dynamics by regulating the PYK/paxillin/CAS pathway.

Role of CAS-mediated process in actin filament assembly in smooth muscle

Crk-associated substrate (CAS) is a 130-kDa focal adhesion protein that was originally identified as a prominent tyrosine-phosphorylated protein in v-src and v-crk transformed cells ⁵⁵^,⁵⁶. Molecular analysis of CAS revealed a docking protein that contains an SH3 domain, proline-rich regions, and a substrate domain containing multiple Tyr-Xaa-Xaa-Pro (YXXP) ⁵⁶^,⁵⁷. CAS has been shown to regulate the actin cytoskeleton in smooth muscle. The downregulation of CAS by antisense oligonucleotides dramatically attenuates force development and actin polymerization in response to contractile stimulation ⁷. CAS undergoes tyrosine phosphorylation in vascular smooth muscle cells in response to stimulation with angiotensin II and serotonin ⁵⁸^,⁵⁹ as well as in non-muscle cells including rat-1 cells, COS-7 cells, and CE cells in response to growth factors and cell adhesion ⁵⁷^,⁶⁰^,⁶¹. Phosphorylation of CAS increases its binding to the adapter protein CrkII ²⁵^,⁵⁷. In smooth muscle, contractile stimulation leads to the increase in the association of CrkII with N-WASP. When unstimulated, the C-terminal portion of N-WASP binds to its GTP-binding domain, masking its binding motif for the Arp2/3 complex. The interaction of CrkII with N-WASP induces conformational changes, exposing the binding motif for the Arp2/3 complex and initiating actin polymerization and branching mediated by the Arp2/3 complex ¹⁰^,¹²^,¹³^,²⁵^,²⁷^,³⁹^,⁶².

Profilin is an actin-associated protein that regulates actin dynamics, the organization of actin filaments and smooth muscle force development. In vitro studies have shown that profilin binds to actin monomers and transport monomers onto the barbed end of actin filaments. Profilin may also promote the nucleation of actin filament polymerization mediated by N-WASP and the Arp2/3 complex ⁶³^,⁶⁴. In carotid smooth muscle preparations, contractile activation promotes the association of profilin with G-actin. Moreover, the downregulation of CAS blocks the formation of profilin/G-actin coupling, actin polymerization and tension development. These results suggest that CAS may regulate actin dynamics by affecting the activity of profilin ⁶^,⁷^,⁵⁹.

The tyrosine phosphorylation of CAS is mediated by Abl, a non-receptor tyrosine kinase. Studies from in vitro biochemical assay showed that CAS phosphorylation is catalyzed directly by Abl ²⁵^,⁶⁵. Silencing of Abl by short hairpin RNA dramatically depresses CAS phosphorylation in resistance arteries upon contractile stimulation ²⁵^,⁵⁹. Furthermore, Abl in vascular smooth muscle is activated by agonist stimulation; the phosphorylation of Abl at Tyr-412 (an index of kinase activation) is enhanced in stimulated arteries compared to unstimulated tissues ²⁵. Abl tyrosine phosphorylation has also been reported in vascular smooth muscle cells upon angiotensin II stimulation ⁶⁶. Interestingly, a selective inhibitor of Abl, imatinib (STI-571), has been recently shown to be effective for the treatment of pulmonary hypertension in clinical studies ⁶⁷^,⁶⁸.

FAK and Src family tyrosine kinase mediated cytoskeletal remodeling

FAK and c-Src are located at the integrin-associated membrane microdomain and are activated by integrin clustering as well as activation with contractile agonists and growth factors ²²^,²³^,⁶⁹^-⁸⁰. FAK has been shown to catalyze phosphorylation of the cytoskeletal protein paxillin in vitro and in airway smooth muscle tissues ²³^,⁶⁹^,⁸¹^-⁸³. Although similar studies on vascular smooth muscle have not been pursued, it is generally believed that vascular and airway smooth muscles share similar intracellular regulatory mechanisms. Paxillin also undergoes tyrosine phosphorylation in vascular smooth muscle preparations during agonist stimulation ¹⁶. Paxillin may be involved in the regulation of N-WASP that mediates actin dynamics and/or structural re-array of the actin cytoskeleton in various cell types including smooth muscle cells ¹⁰^-¹²^,¹⁶^,²²^,³⁵^,⁸¹^,⁸⁴^-⁸⁷.

c-Src has been reported to mediate CAS phosphorylation in vascular smooth muscle; inhibition of Src activity attenuates CAS tyrosine phosphorylation upon agonist activation ⁵⁹. As described earlier, CAS phosphorylation regulates actin filament assembly mediated by the Arp2/3 complex. Src may modulate CAS phosphorylation by affecting the activity of Abl ²⁵^,⁶⁶. However, other studies suggest that Src may be responsible for integrin-mediated tyrosine phosphorylation of CAS ⁸⁸^,⁸⁹. In addition, the activated c-Src interacts with FAK to mediate the regulation of basal Ca²⁺ channel activity and the platelet-derived growth factor (PDGF)-induced increase in L-type Ca²⁺ current ⁴^,⁹⁰.

Integrin-mediated signaling cascades in the modulation of actin dynamics

Transmembrane integrins are cell surface receptors that have been shown to serve as mechanical sensors in cells. In smooth muscle cells, integrins are located in membrane-associated dense plaques that are structurally analogous to focal adhesions of cultured cells ¹^,⁴^,²². As discussed earlier, β-integrins interact with extracellular matrix on the outside of the membrane and link to actin filaments in the inside of the membrane. The structural linkage of matrix to the actin cytoskeleton by integrins facilitate mechanical force transmission between the contractile apparatus and extracellular matrix ¹^,⁴^,²²^,²³^,³⁵^,⁵⁰.

Integrins are able to sense mechanical signals in the environment, and to transduce the signals onto intracellular pathways that regulate remodeling of the actin cytoskeleton. FAK, c-Src, protein tyrosine kinase 2 (Pyk2), CAS, and paxillin are associated with integrins on the membrane. FAK is activated by autophosphorylation at Tyr-397 in response to ligand binding to integrins ⁴^,⁹¹^,⁹². Both FAK and c-Src become phosphorylated in nonmuscle cells (e.g. endothelial cells and leukocytes) stimulated by adhesion-mediated integrin activation ⁴^,⁹¹^-⁹⁴. Integrin activation may also stimulate FAK and c-Src in smooth muscle; the tyrosine phosphorylation of FAK and paxillin is mechanosensitive (integrin is a known mechanosensor) in smooth muscle ²²^,²³. Cyclic strain activates Pyk2 and FAK phosphorylation at focal adhesion sites in cells ⁹⁵. The integrin-mediated activation of tyrosine kinases in turn modulates the functional status of downstream molecules such as paxillin and Hic-5 that are related to remodeling of the actin architecture ⁴^,⁵^,⁴¹^,⁹⁴^,⁹⁵.

Conversely, the reorganization of the actin cytoskeleton may influence the clustering of integrins and engagement of integrins with extracellular matrix. There is evidence to show that stress fiber formation affects the aggregation of integrins on the membrane ⁹⁶. Treatment of smooth muscle cells with contractile agonists leads to the increase in resistance of integrin-bound beads, indicating enhancement of the matrix-integrin association ⁴^,²⁰. The “inside-out” signaling may provide a positive feedback to dense plaques, render integrins poised to respond to next mechanical signals.

The integrin-activated FAK and c-Src have also been linked to the regulation of Ca²⁺ signaling in differentiated smooth muscle cells. The inhibition of c-Src attenuates the increase in Ca²⁺ current activated by α₅-integrin antibody or fibronectin whereas the inhibition of tyrosine phosphatase enhances the integrin-mediated intracellular Ca²⁺ ⁹⁷. The integrin-stimulated enhancement of Ca²⁺ current is also depressed when cells are dialyzed with antibodies against FAK or c-Src ⁴^,⁹⁷. In addition to activation of the contractile protein myosin, the FAK/Src-mediated increase in intracellular Ca²⁺ may also activate protein tyrosine kinase 2 (PYK2) that is able to catalyze CAS and/or paxillin phosphorylation and regulates the actin cytoskeleton ⁴^,⁶⁹^,⁹⁵^,⁹⁷^-¹⁰².

Small GTPases and actin architecture in smooth muscle

The Rho family of the small GTPases consists primarily of Rho, Cdc42, and Rac. Rho may mediate agonist-induced actin stress fiber formation in cultured smooth muscle cells. Treatment with C3 exoenzyme (inactivator of Rho) diminished the agonist-induced increase in F/G-actin ratios as estimated by cytofluorescence microscopy. This was reported to be mediated by G_q and G_i in smooth muscle cells ⁵^,¹⁷^,¹⁰³. Rho may also regulate actin cytoskeleton remodeling via the Rho kinase/LIM kinase/cofilin pathway. Cofilin is an actin-regulatory protein that triggers actin filament depolymerization; phosphorylation of cofilin by LIM kinase inhibits its ability to depolymerize actin filaments. Rho kinase induces the phosphorylation of LIM kinase, which enhances LIM kinase activity towards cofilin and promotes cofilin phosphorylation and actin filament assembly ¹⁰⁴^-¹⁰⁷. Rho may also modulate actin dynamics by affecting Mammalian Diaphanous-related (mDia) formins that nucleate, progressively elongate and bundle actin filaments ¹⁰⁸^-¹¹⁰. Further studies are needed to assess whether the Rho-mediated actin dynamics occurs in intact vascular smooth muscle tissues.

There is a wealth of evidence that Cdc42 regulates actin filament polymerization in various cell types including smooth muscle cells ¹²^,¹¹¹^-¹¹⁵. GTP bound form of Cdc42 (activated Cdc42) binds to the GTP binding domain of N-WASP, inducing a conformational change and activating N-WASP, and triggering the nucleation of actin polymerization and actin filament branching ¹⁰^,¹²^,²⁷^,⁴⁰^,¹¹⁶. In smooth muscle tissues, introduction of a dominant Cdc42 mutant depresses the activity of N-WASP concurrently with the decrease in actin polymerization and force development ¹⁰^,¹², suggesting that Cdc42-mediated actin filament assembly is essential for smooth muscle contraction.

Cdc42 and Rac are known to activate p21-activated kinase (PAK) in mammalian cells ¹¹⁷^-¹²¹. Although 6 isoforms have been found thus far, PAK1 is a major isoform in smooth muscle cells ¹¹⁷^-¹¹⁹^,¹¹⁹^,¹²⁰^,¹²²^,¹²³. PAK has been shown to participate in the regulation of p38 MAP kinase in smooth muscle upon activation with the growth factor ¹¹⁷. The activation of p38 MAP kinase may modulate the actin cytoskeleton and cell migration via heat shock protein (HSP) ¹¹⁷^,¹²⁴^,¹²⁵(See below).

The small GTPases are activated by contractile agonists as well as integrin aggregation. Cdc42 activation has been observed in smooth muscle tissues in response to contractile stimulation ¹⁰^,¹². Chemical stimulation also induced Rho activation in vascular smooth muscle tissues ¹²⁶^-¹²⁸. Attachment of cells to fibronectin leads to activation of both Cdc42 and Rac. Rho is also activated by integrin ligation, resulting in the formation of stress fiber ⁹⁶. In addition, cyclic strain induces reorganization of actin stress fibers, which may be mediated by the small GTPase Rho ²⁶^,¹²⁹.

Role of small heat shock proteins in smooth muscle

In addition to providing protection against physical and chemical stresses, HSP27 (heat shock protein 27) may participate in the regulation of the actin cytoskeleton ⁴^,⁵. In vitro biochemical studies have shown that unphosphorylated HSP25 (mouse and chicken homologs of HSP27) inhibits actin polymerization as assessed by fluorescence spectroscopy and electron microscopy. Phosphorylated HSP27 loses the ability to inhibit actin filament assembly ⁴^,¹²⁹^-¹³¹. Signaling cascades regulating HSP27 phosphorylation has been documented. In non-muscle cells, HSP27 is phosphorylated by MAP kinase-activated protein (MAPKAP) kinase 2 (MK2) that is activated by phosphorylation mediated by p38 MAP kinase. Upstream regulators of p38 MAP kinase includes PAK and other kinases ⁴^,⁵. Smooth muscle seems to share similar signaling pathways to phosphorylate HSP27 during contractile activation ⁴^,¹²⁴.

HSP27 is thought to regulate the actin cytoskeleton in differentiated smooth muscle because of high-level expression of the protein in smooth muscle and spatial localization with contractile proteins ⁴^,¹³². There is evidence to show that HSP27 is associated with the cellular processes that orchestra smooth muscle contraction. In permeabilized smooth muscle preparations, agonist-induced contraction was inhibited by antibodies against HSP27 ⁵^,¹³³^,¹³⁴. Moreover, agonist activation induced HSP27 phosphorylation in smooth muscle tissues, which was blocked by a p38 MAP kinase inhibitor. The depression of HSP27 phosphorylation inhibited angiotensin II-induced vasoconstriction ⁴.

Another heat shock protein HSP20 was reported to be phosphorylated at Ser-16 in vascular smooth muscle tissues by the treatment with forskolin. Forskolin is known to increase the cellular concentration of cAMP that is able to activate protein kinase A (PKA). HSP20 phosphorylation was associated with the decrease in force development in vascular smooth muscle. However, phosphorylation of HSP20 seems not to depolymerize filamentous actin in swine carotid artery. Further studies are needed to elucidate the role of HSP20 phosphorylation in the actin cytoskeleton and smooth muscle contraction ⁴^,¹⁵.

Perspectives

Understanding the molecular mechanisms by which chemical and mechanical stimuli initiate tension development in vascular smooth muscle may disclose new biological targets for the development of more effective treatment of cardiovascular diseases. Actin filament polymerization has recently emerged as an essential cellular event that substantially regulates force development in vascular smooth muscle. A pool of G-actin polymerizes onto existing actin filaments in smooth muscle in response to chemical and mechanical stimulation. There is compelling evidence that the inhibition of actin assembly depresses smooth muscle contraction. Changes in chemical and mechanical environments surrounding smooth muscle activate several important signaling pathways that involve protein kinases, integrins, small GTPases, and actin-associated molecules. These pathways are critical for the regulation of actin dynamics and force development; intervention of the signaling cascades affects smooth muscle contraction.

Acknowledgments

This work was supported by The National Heart, Lung, and Blood Institute Grant HL-75388

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PERMALINK

Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle

Dale D Tang, MD & PhD

Yana Anfinogenova, PhD

Abstract

Introduction

Figure 1. Schematic illustration of the actin cytoskeleton in smooth muscle cells.

Physiologic properties of the actin cytoskeleton in arterial smooth muscle

Actin filament polymerization occurs in response to contractile and mechanical stimulation

Actin filament assembly participates in contractile force development

Cellular processes regulating actin dynamics in smooth muscle

Figure 2. Signaling cascades for the regulation of actin dynamics in smooth muscle.

Role of CAS-mediated process in actin filament assembly in smooth muscle

FAK and Src family tyrosine kinase mediated cytoskeletal remodeling

Integrin-mediated signaling cascades in the modulation of actin dynamics

Small GTPases and actin architecture in smooth muscle

Role of small heat shock proteins in smooth muscle

Perspectives

Acknowledgments

References

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Cite

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PERMALINK

Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle

Dale D Tang, MD & PhD

Yana Anfinogenova, PhD

Abstract

Introduction

Figure 1. Schematic illustration of the actin cytoskeleton in smooth muscle cells.

Physiologic properties of the actin cytoskeleton in arterial smooth muscle

Actin filament polymerization occurs in response to contractile and mechanical stimulation

Actin filament assembly participates in contractile force development

Cellular processes regulating actin dynamics in smooth muscle

Figure 2. Signaling cascades for the regulation of actin dynamics in smooth muscle.

Role of CAS-mediated process in actin filament assembly in smooth muscle

FAK and Src family tyrosine kinase mediated cytoskeletal remodeling

Integrin-mediated signaling cascades in the modulation of actin dynamics

Small GTPases and actin architecture in smooth muscle

Role of small heat shock proteins in smooth muscle

Perspectives

Acknowledgments

References

ACTIONS

PERMALINK

RESOURCES

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