β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

Sharma, Pawan; Ghavami, Saeid; Stelmack, Gerald L.; McNeill, Karol D.; Mutawe, Mark M.; Klonisch, Thomas; Unruh, Helmut; Halayko, Andrew J.

doi:10.1242/jcs.066712

Cited by 49 publications

(59 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). This co-alignment of caveolae with stress fibers has been observed in many cell types, including fibroblasts (Röhlich and Allison, 1976;Singer, 1979;Rothberg et al, 1992), myofibroblasts (Valentich et al, 1997), epithelial cells (Mundy et al, 2002;Echarri et al, 2012) and muscle cells (Sharma et al, 2010). However, such a co-alignment is not observed in all cells that have prominent stress fibers.…”

Section: Introductionmentioning

confidence: 74%

“…Dystrophin localizes to caveolae-enriched areas in smooth muscle cells (North et al, 1993) and can be detected in Cav3 immunoprecipitates (Doyle et al, 2000). Notably, independent studies have shown that Cav3 and Cav1 bind to β-dystroglycan (Sotgia et al, 2000;Sharma et al, 2010). Muscle-specific filamin A has been shown to interact with sarcoglycans, a family of dystrophin-associated glycoproteins, indicating that filamin A could link Cav3 to the DGC (Thompson et al, 2000).…”

Section: Cav1 Is Functionally Linked To the Extracellular Matrixmentioning

confidence: 99%

See 1 more Smart Citation

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Echarri

Pozo

2015

Journal of Cell Science

170

209

View full text Add to dashboard Cite

An essential property of the plasma membrane of mammalian cells is its plasticity, which is required for sensing and transmitting of signals, and for accommodating the tensional changes imposed by its environment or its own biomechanics. Caveolae are unique invaginated membrane nanodomains that play a major role in organizing signaling, lipid homeostasis and adaptation to membrane tension. Caveolae are frequently associated with stress fibers, a major regulator of membrane tension and cell shape. In this Commentary, we discuss recent studies that have provided new insights into the function of caveolae and have shown that trafficking and organization of caveolae are tightly regulated by stress-fiber regulators, providing a functional link between caveolae and stress fibers. Furthermore, the tension in the plasma membrane determines the curvature of caveolae because they flatten at high tension and invaginate at low tension, thus providing a tension-buffering system. Caveolae also regulate multiple cellular pathways, including RhoA-driven actomyosin contractility and other mechanosensitive pathways, suggesting that caveolae could couple mechanotransduction pathways to actin-controlled changes in tension through their association with stress fibers. Therefore, we argue here that the association of caveolae with stress fibers could provide an important strategy for cells to deal with mechanical stress.

show abstract

Section: Introductionmentioning

confidence: 74%

Section: Cav1 Is Functionally Linked To the Extracellular Matrixmentioning

confidence: 99%

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Echarri

Pozo

2015

Journal of Cell Science

170

209

View full text Add to dashboard Cite

show abstract

“…Caveolins are a key component of the caveolae in smooth muscle, which act to regulate many major membrane functions, including organizing cell signaling components and vesicular trafficking (18,35,36,55). They have been shown to participate in excitation-contraction coupling in gut, vascular, and airway smooth muscle, but they have also been shown to have a role in the controlling relaxation pathways, particularly those involving NO (2,4,20,37,46,50).…”

Section: Discussionmentioning

confidence: 99%

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Mahavadi

Bhattacharya²,

Kumar³

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Murthy KS. Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1 Ϫ/Ϫ mice impair the peristaltic reflex and propulsion. Am J Physiol Gastrointest Liver Physiol 305: G964 -G974, 2013. First published October 24, 2013 doi:10.1152/ajpgi.00165.2013.-Caveolae are specialized regions of the plasma membrane that concentrate receptors and associated signaling molecules critical in regulation of cellular response to transmitters and hormones. We have determined the effects of caveolin-1 (Cav-1) deletion, caveolin-1 siRNA, and caveolar disruption in mice on the signaling pathways that mediate contraction and relaxation in colonic smooth muscle and on the components of the peristaltic reflex in isolated tissue and propulsion in intact colonic segments. In Cav-1 Ϫ/Ϫ mice, both relaxation and contraction were decreased in smooth muscle cells and muscle strips, as well as during both phases of the peristaltic reflex and colonic propulsion. The decrease in relaxation in response to the nitric oxide (NO) donor was accompanied by a decrease in cGMP levels and an increase in phosphodiesterase 5 (PDE5) activity. Relaxation by a PDE5-resistant cGMP analog was not affected in smooth muscle of Cav-1 Ϫ/Ϫ mice, suggesting that inhibition of relaxation was due to augmentation of PDE5 activity. Similar effects on relaxation, PDE5 and cGMP were obtained in muscle cells upon disruption of caveolae by methyl-␤-cyclodextrin or suppression of Cav-1. Sustained contraction mediated via inhibition of myosin light chain phosphatase (MLCP) activity is regulated by Rho kinase and PKC via phosphorylation of two endogenous inhibitors of MLCP: myosin phosphatasetargeting subunit (MYPT1) and 17-kDa PKC-potentiated protein phosphatase 1 inhibitor protein (CPI-17), respectively. The activity of both enzymes and phosphorylation of MYPT1 and CPI-17 were decreased in smooth muscle from Cav-1 Ϫ/Ϫ mice. We conclude that the integrity of caveolae is essential for contractile and relaxant activity in colonic smooth muscle and the maintenance of neuromuscular function at organ level.caveolin; phosphodiesterase; Rho kinase; smooth muscle; peristaltic reflex CAVEOLAE AND THEIR MAIN MEMBRANE PROTEINS, caveolin-1 (Cav-1), -2, and -3, form regular invaginations of the plasma membrane, which are sites that concentrate receptors, G proteins, effector enzymes, and associated signaling molecules in several cell types (reviewed in Refs. 2, 4, 22, 37, 50). As such, they play a critical role in regulating, either by augmenting or inhibiting, the physiological response of cells to transmitters and hormones. Most studies have concentrated on identifying their role in regulating the response to agonists at the cellular level; however, the translation of these cellular effects of caveolin to the organ level is less well understood although many roles have been postulated (1, 25, 43-45, 50, 58).In the gut, caveoli are present on many cell types, including smooth muscle cells, interstitial cells of Cajal (ICC), and endothelial cell...

show abstract

“…To date, four cavins have been identified: PTRF/cavin1 (21,58), SDPR/cavin2 (19), SRBC/ cavin3 (36), and MURC/cavin4 (2, 37). There is currently limited information on cavins in ASM or airway in general (49). Furthermore, species and cell type differences may be relevant but have not been studied.…”

Section: Effect Of Cav1 Ko On Airway Mechanicsmentioning

confidence: 99%

Caveolin-1 knockout mice exhibit airway hyperreactivity

Aravamudan

VanOosten

Meuchel

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Although caveolins have been found in endothelium and epithelium (where they regulate nitric oxide synthase activity), their role in smooth muscle is still under investigation. We and others have previously shown that caveolae of human airway smooth muscle (ASM), which express caveolin-1, contain Ca 2ϩ and force regulatory proteins and are involved in mediating the effects of inflammatory cytokines such as TNF-␣ on intracellular Ca 2ϩ concentration responses to agonist. Accordingly, we tested the hypothesis that in vivo, absence of caveolin-1 leads to reduced airway hyperresponsiveness, using a knockout (KO) (Cav1 KO) mouse and an ovalbumin-sensitized/challenged (OVA) model of allergic airway hyperresponsiveness. Surprisingly, airway responsiveness to methacholine, tested by use of a FlexiVent system, was increased in Cav1 KO control (CTL) as well as KO OVA mice, which could not be explained by a blunted immune response to OVA. In ASM of wild-type (WT) OVA mice, expression of caveolin-1, the caveolar adapter proteins cavins 1-3, and caveolae-associated Ca 2ϩ and force regulatory proteins such as Orai1 and RhoA were all increased, effects absent in Cav1 KO CTL and OVA mice. However, as with WT OVA, both CTL and OVA Cav1 KO airways showed signs of enhanced remodeling, with high expression of proliferation markers and increased collagen. Separately, epithelial cells from airways of all three groups displayed lower endothelial but higher inducible nitric oxide synthase and arginase expression. Arginase activity was also increased in these three groups, and the inhibitor nor-NOHA (N-omega-nor-L-arginine) enhanced sensitivity of isolated tracheal rings to ACh, especially in Cav1 KO mice. On the basis of these data disproving our original hypothesis, we conclude that caveolin-1 has complex effects on ASM vs. epithelium, resulting in airway hyperreactivity in vivo mediated by altered airway remodeling and bronchodilation. Overall, in vitro data clearly demonstrate an important role for caveolin-1 in enhanced airway contractility relevant to asthma. However, the effect of altered caveolin-1 expression or function in vivo has not been examined and was the focus of this study. Based on previous work, our hypothesis was that reduced caveolin-1 results in airway hyporesponsiveness. To this end we employed the mouse lacking caveolin-1 (Cav1 KO) as a model, with ovalbumin (OVA) sensitization and challenge as a model of allergic airway hyperresponsiveness to test our hypothesis. Cav1 KO mice are known to develop pulmonary fibrosis (9,15,60), and a single study showed that these mice have reduced lung compliance and increased elastance by 3 mo of age (28), with evidence of progressively greater deposition of collagen within airways and parenchyma. Whether such changes are associated with altered airway contractility and the specific role of ASM per se have not been examined. In the present study, we compared airway structure and function in wild-type (WT) vs. Cav1 KO mice that were either unsensitized [control (CTL)] or sensitiz...

show abstract

β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

Cited by 49 publications

References 63 publications

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion

Caveolin-1 knockout mice exhibit airway hyperreactivity

Contact Info

Product

Resources

About

β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

Cited by 49 publications

References 63 publications

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Caveolae – mechanosensitive membrane invaginations linked to actin filaments

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1−/− mice impair the peristaltic reflex and propulsion

Caveolin-1 knockout mice exhibit airway hyperreactivity

Contact Info

Product

Resources

About

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1^−/− mice impair the peristaltic reflex and propulsion