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Smooth Muscle Excitation-Contraction Coupling: a Role for Caveolae and Caveolins?

Michael J. Taggart

M. J. Taggart is in the Department of Medicine and Maternal and Fetal Health Research Centre, University of Manchester, Manchester Royal Infirmary, Manchester M13 9WL, England.

	Abstract

 
Agonist stimulation of smooth muscle contractility involves integration of many signal-transducing events from the plasma membrane to myofilaments in the cytoplasm. Recent evidence suggests an important role for membranous invaginations termed caveolae, and their integral protein components caveolins, in the coordination of extracellular contractile stimuli and intracellular effectors in smooth muscle.

	Introduction

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 
Caveolae are flask-shaped invaginations of the plasma membrane that are abundant features of smooth muscle. Following their initial description in epithelial cells almost 50 years ago (15) many diverse functional roles have been ascribed to caveolae, including regulation of macromolecular transport, particularly cholesterol deposition, cell volume regulation, and Ca²⁺ homeostasis. The discovery in the early 1990s of caveolins, a family of proteins critical to caveolar formation that, in vitro, interact with a variety of signal-transducing molecules, has highlighted an additional possible function of caveolae: as sites of integration of events linking extracellular stimuli and intracellular effectors.

	Smooth muscle contractile regulation

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 
A stimulus-induced increase in the concentration of intracellular Ca²⁺ ([Ca²⁺]_i) is the prime modulator of smooth muscle contractility. The major source of this [Ca²⁺]_i elevation arises from transsarcolemmal Ca²⁺ influx, but the sarcoplasmic reticulum (SR) is also a prominent intracellular store of releasable Ca²⁺ used for smooth muscle contractile activation. The Ca²⁺ released from the SR [via inositol 1,4,5-trisphosphate (IP₃)-induced Ca²⁺ release and/or via transsarcolemmal Ca²⁺-induced Ca²⁺ release] can either directly activate the contractile filaments or indirectly alter the excitability of the cell by affecting ion channel activity in the plasma membrane.

In addition to altering [Ca²⁺]_i, receptor-coupled activation of smooth muscle contractility involves a sensitization of the myofilaments to the activating Ca²⁺ (11). The primary mechanism of force generation is the Ca²⁺- and calmodulin-dependent phosphorylation of the regulatory myosin light chains (MLC₂₀) by MLC kinase. MLC₂₀ dephosphorylation by MLC phosphatase precedes relaxation, and both the kinase and phosphatase are under regulatory influences. RhoA and protein kinase C (PKC)-, two intracellular proteins acting downstream of receptor activation, have been proposed to be important mediators of smooth muscle contractility. Both molecules have been suggested to sensitize the contractile filaments to Ca²⁺ by separate upstream mechanisms, which, however, converge downstream by inhibiting MLC phosphatase activity (thereby increasing MLC₂₀ phosphorylation and force). The effects of rhoA appear to be mediated in large part via activation of the effector molecule rho-associated kinase (ROK). Recently, with the use of immunofluorescent laser scanning confocal microscopy and subsequent digital image analysis, we quantified the distributions of rhoA, ROK, and PKC- in isolated, intact, contractile smooth muscle cells. Agonist stimulation resulted in significant redistribution of all three molecules from the cytoplasm to the cell periphery (12). These results were consistent with the suggestions that membranous relocalization of rhoA and PKC- was a necessary step for receptor-induced Ca²⁺ sensitization of force. Furthermore, receptor-coupled Ca²⁺-sensitization occurred in these cells without significant redistribution of ROK away from the membrane (12). An intriguing possibility, therefore, was that caveolae may be involved in the stimulus-dependent alterations of smooth muscle [Ca²⁺]_i and the relocation of contractile regulatory signal-transducing molecules to the plasma membrane.

	Caveolae morphology in smooth muscle

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 
Caveolae are 50- to 90-nm flask-shaped invaginations that appear in rows in periodic register along the longitudinal axis of the smooth muscle membrane, interspersed by regions of dense bodies anchoring the cytoskeleton, as illustrated in Fig. 1A. Caveolae thus constitute a substantial proportion of the smooth muscle cell membrane, increasing the surface area by up to 75% (2, 10). Developmental changes in smooth muscle caveolae are evident with increasing density throughout embryogenesis and adulthood up to ~35/µm². Exogenous markers penetrate the caveolar invagination, indicating that the necks of caveolae can be in free contact with the extracellular space. Compared with other cell types, smooth muscle caveolae have thus been suggested to be relatively static structures. However, although usually appearing as singular invaginations, multiple caveolae can fuse to offer a tube-like appearance. Although caveolar density may not change in response to physiological levels of smooth muscle stretch (2), it is still a matter of debate whether they act as sensors to stretch and/or volume changes via a widening of the neck region, leading to a more flattened appearance (7). However, this does not appear to be the case with physiological hypertrophy (e.g., uterine smooth muscle of pregnant rat in Fig. 1A) or experimental hypertrophy of smooth muscle cells, where caveolae assume a normal appearance.

View larger version (103K): [in this window] [in a new window]   FIGURE 1. Smooth muscle caveolae. A: conventional electron micrograph of rat uterine smooth muscle indicating rows of caveolae (CV) adjacent to dense bodies (DB). Scale bar = 0.3 µm. B: electron micrograph of rat portal vein treated with osmium ferricyanide. The sarcoplasmic reticulum (SR) is stained black. Arrows denote close association of the peripheral SR and caveolae at the plasma membrane. Scale bar = 1 µm. Inset: enlarged representation of caveolae encircled by the SR network (denoted by arrows). Scale bar = 0.5 µm. Figure courtesy of Graeme Nixon and Paul Tasker.

	Caveolin expression and localization in smooth muscle

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

View larger version (13K): [in this window] [in a new window]   FIGURE 2. Caveolin localization in isolated smooth muscle. Single uterine smooth muscle cells isolated from pregnant rat were fixed, permeabilized, and stained for caveolin-1, -2, or -3 with isoform-specific antibodies. Laser scanning confocal microscopic analysis of central cell sections indicated that each caveolin isoform was predominantly located at the plasma membrane. Scale bar = 10 µm.

	Caveolae and smooth muscle [Ca2+]i homeostasis.

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

Mitochondria are often also observed in proximity to caveolae, and the SR can neatly encircle these organelles too (5). Such close geometric relationships between caveolae and intracellular organelles such as the SR, mitochondria, and nucleus may be advantageous in allowing smooth muscle to tightly regulate [Ca²⁺]_i fluxes (see below), energy use, and gene expression.

Early electron microscopic studies of smooth muscle suggested that significant Ca²⁺ deposition occurred in caveolae. In addition, freeze fracture investigations indicated a prominent clustering of intramembrane particles close to the neck of caveolae (2, 10), and striations on smooth muscle caveolae have also been reported (7, 10). The subsequent use of different experimental methodologies, although a cautionary note should be made of the limitations of each, has led to the identification of several proteins likely to be resident in smooth muscle caveolae. Immunoelectron microscopy studies localized both a Ca²⁺-ATPase and an IP₃-like receptor to smooth muscle caveolae (1). Subcellular fractionation and immunoprecipitation data of cultured smooth muscle also suggests caveolar accumulation of receptors for contractile agents (e.g., bradykinin) linked to phosphoinositide hydrolysis (14). Additionally, high resolution light microscopy data suggested that the Na⁺/Ca²⁺ exchanger, the activity of which is closely influenced by SR-releasable Ca²⁺, may be enriched in caveolar regions of the smooth muscle membrane (4). As such, the residence of caveolae adjacent to the SR, commonly separated by distances as little as 10–40 nm, together with the caveolar localization of proteins important for Ca²⁺ mobilization and transport, supports the notion that these plasmalemmal structures may be influential in the regulation of smooth muscle Ca²⁺ homeostasis. It is noteworthy that, in constantly perfused cultured endothelial cells, agonist-induced (e.g., bradykinin) increases in [Ca²⁺]_i, originating from endoplasmic reticular Ca²⁺ release, occurred at specific loci towards the cell periphery directly opposite plasma membranous areas rich in caveolin and, therefore, presumably containing caveolae (3). Given the reported increased intensity of caveolin staining at the cell extremities (13), and of regions opposite the nucleus, it will be of great interest to establish whether such a phenomenon exists in smooth muscle.

	In vitro interactions of caveolins and signal transduction molecules

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 
Cell-free studies have indicated that caveolins interact with a variety of signal-transducing molecules and regulate their activity, including PKC-, rhoA, Raf, mitogen-activated protein kinase, G subunits, and receptor-dependent tyrosine kinases (reviewed in Refs. 6 and 8). A short NH₂ terminal cytoplasmic region of caveolin-1 (residues 82–101) was found to be critical for these regulatory interactions and was termed the "scaffolding domain." Analogous regions exist in caveolins-2 and -3. Indeed, the scaffolding domain of caveolin-3 has also been shown to regulate the activity of the catalytic domain of PKC-.

	Caveolin scaffolding domain and smooth muscle signaling proteins

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 
As mentioned above, the caveolin-1 scaffolding domain is a region crucial for the regulatory interaction with diverse signal-transducing molecules in in vitro biochemical studies, including PKC- and rhoA. Indeed, use of the caveolin-1 scaffolding domain to select peptide ligands from bacteriophage display libraries allowed the identification of amino acid motifs (XXXXX and XXXXXX, where = aromatic amino acid) characteristic of many signaling proteins suggested to interact with caveolins (6). Such sequences are contained within the catalytic domain of PKC- (⁵²²WAYGVLLY⁵²⁸), the switch I region of rhoA (³⁴YVPTVFENY⁴²), and the catalytic domain of ROK- (¹⁵¹WVVQLFCAF¹⁵⁹ and ¹⁶⁴YLYMVMEY¹⁸¹). In particular, the sites of monoglucosylation and ADP ribosylation of rhoA, modifications of functional importance because they result in inhibition of agonist-induced Ca²⁺ sensitization and/or rhoA translocation, are contained within the putative caveolin-binding motif of rhoA. This sequence of rhoA is also contained within a region of the molecule thought to be important for interaction with ROK.

In addition, the caveolin-1 scaffolding domain peptide assumes a homogeneous distribution throughout the cytoplasm when chemically loaded into single isolated smooth muscle cells. Under these circumstances, agonist-induced translocations of rhoA and PKC- from the cytoplasm to the cell membrane are completely inhibited (see Fig. 3), an effect not observed in sham-treated cells or cells loaded with a scrambled peptide (13). These results further support the notion that there is a direct interaction between the scaffolding domain region of caveolin(s) and rhoA and PKC- in intact contractile smooth muscle. Although the influence of the scaffolding domain peptides of caveolins-2 and -3 on the activities of various signaling molecules has been examined in other cell types, their effects on membranous recruitment of rhoA and PKC- in smooth muscle remains unresolved. The seemingly ubiquitous expression of each caveolin isoform in smooth muscle, and the consequent possibility (as yet undetermined) of caveolin-specific caveolae, may thus allow for a spatial selectivity of multiple signal transduction pathways.

View larger version (21K): [in this window] [in a new window]   FIGURE 3. The scaffolding domain peptide of caveolin-1 inhibits agonist-induced redistribution of protein kinase C (PKC)- and rhoA in smooth muscle cells. PKC- and rhoA distributions were assessed in isolated smooth muscle cells by immunofluorescent confocal microscopy (13). Carbachol (cch) stimulation of control cells resulted in significant redistribution of PKC- and rhoA from the cytosol to the cell periphery, as indicated by increases in the peripheral:cytosolic ratio. Such translocation of PKC- and rhoA was completely inhibited in cells treated with the scaffolding domain peptide of caveolin-1. *P < 0.05.

	Conclusions

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

View larger version (31K): [in this window] [in a new window]   FIGURE 4. Diagrammatic representation of proposed events occurring at caveolae during agonist stimulation of smooth muscle. Agonist stimulation of smooth muscle results in caveolar accumulation of transmembrane receptors (-R) coupled to inositol 1,4,5-trisphosphate (IP3) production, consistent with the localization of an IP3-like receptor to caveolae. Localized IP3 production results in Ca2+ release from the closely underlying SR, resulting in contractile activation. A portion of this released Ca2+ is removed from the cytosol by the Na+/Ca2+ exchanger suggested to be enriched in caveolae. Receptor stimulation also results in translocation to the cell periphery of signaling molecules important for Ca2+ sensitization of force, including rhoA and PKC-. Inhibition of such translocation by the caveolin scaffolding domain peptide indicates that caveolins, and thus caveolae, are involved in the membranous recruitment of signaling molecules acting downstream of contractile receptor activation. ROK, rho-associated kinase.

NOTE ADDED IN PROOF
Recently, Löhn et al. (Circ Res 87: 1034–1039, 2000) have treated arterial smooth muscle cells with a cholesterol-depleting agent and observed a reduction of the frequency and dimensions of spontaneous Ca²⁺ sparks, localized releases of SR Ca²⁺. These functional changes were suggested to be due to an alteration in the structural arrangement of caveolae and the underlying SR.

	Acknowledgments

 
I thank Graeme Nixon and Paul Tasker (Department of Biomedical Sciences, University of Aberdeen) for kindly providing the electron micrograph of Fig. 1B and Dr. Clare Austin (Department of Medicine, University of Manchester) for critical reading of the manuscript.

I apologize for the exclusion, due to editorial restrictions, of innumerable excellent articles related to the subject of this review.

	References

Top Introduction Smooth muscle contractile... Caveolae morphology in smooth... Caveolin expression and... Caveolae and smooth muscle... In vitro interactions of... Caveolin scaffolding domain and... Conclusions References

 

1. Fujimoto T, Nakade S, Miyawaki A, Mikoshiba K, and Ogawa K. Localization of inositol 1,4,5-triphosphate receptor-like protein in plasmalemmal caveolae. J Cell Biol 119: 1507–1513, 1992.[Abstract/Free Full Text]
2. Gabella G and Blundell D. Effect of stretch and contraction on caveolae of smooth muscle cells. Cell Tissue Res 190: 255–271, 1978.[Medline]
3. Isshiki M, Ando J, Korenaga R, Kogo H, Fujimoto T, Fujita T, and Kamiya A. Endothelial Ca²⁺ waves preferentially originate at specific loci in caveolin-rich cell edges. Proc Natl Acad Sci USA 95: 5009–5014, 1998.[Abstract/Free Full Text]
4. Moore EDW, Etter EF, Phillipson KD, Carrington WA, Fogarty KE, Lifshitz LM, and Fay FS. Coupling of the Na⁺/Ca²⁺ exchanger, Na⁺/K⁺ pump and sarcoplasmic reticulum in smooth muscle. Nature 365: 657–600, 1993.[Medline]
5. Nixon GF, Mignery GA, and Somlyo AV. Immunogold localization of inosyitol 1,4,5-triphosphate receptors and characterization of ultrastructural features of the sarcoplasmic reticulum in phasic and tonic smooth muscles. J Muscle Res Cell Motil 15: 682–700, 1994.[Web of Science][Medline]
6. Okamoto T, Schlegel A, Scherer PE, and Lisanti MP. Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane. J Biol Chem 273: 5419–5422, 1998.[Free Full Text]
7. Prescott L and Brightman MW. The sarcolemma of Aplysia smooth muscle in freeze-fracture preparations. Tissue Cell 8: 248–258, 1976.[Medline]
8. Schaul PW and Anderson RGW. Role of plasmalemmal caveolae in signal transduction. Am J Physiol Lung Cell Mol Physiol 275: L843–L851, 1998.[Abstract/Free Full Text]
9. Segal SS, Brett SE, and Sessa WC. Codistribution of NOS and caveolin throughout peripheral vasculature and skeletal muscle of hamsters. Am J Physiol Heart Circ Physiol 277: H1167–H1177, 1999.[Abstract/Free Full Text]
10. Somlyo AP. Excitation-contraction coupling and the ultrastructure of smooth muscle. Circ Res 57: 497–507, 1985.[Free Full Text]
11. Somlyo AP and Somlyo AV. Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol (Lond) 522: 177–185, 2000.[Abstract/Free Full Text]
12. Taggart MJ, Lee YH, and Morgan KG. Cellular redistribution of PKC, rhoA and ROK in smooth muscle following agonist stimulation. Exp Cell Res 251: 92–101, 1999.[Web of Science][Medline]
13. Taggart MJ, Leavis P, Feron O, and Morgan KG. Inhibition of PKC and rhoA translocation in differentiated smooth muscle by a caveolin scaffolding domain peptide. Exp Cell Res 258: 72–81, 2000.[Web of Science][Medline]
14. De Weerd WFC and Leeb-Lundberg LMF. Bradykinin sequesters B2 bradykinin receptors and the receptor-coupled G and Gi in caveolae in DDT1 MF-2 smooth muscle cells. J Biol Chem 272: 17858–17866, 1997.[Abstract/Free Full Text]
15. Yamade E. The fine structure of the gall bladder of the mouse epithelium. J Biophys Biochem Cytol 1: 445–458, 1955.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (36) Citing Articles via Google Scholar Google Scholar Articles by Taggart, M. J. Search for Related Content PubMed PubMed Citation Articles by Taggart, M. J.