Caveolae and Caveolins in the Respiratory System

Abstract

Caveolae are flask-shaped invaginations of the plasma membrane that are present in most structural cells. They owe their characteristic Omega-shape to complexes of unique proteins, the caveolins, which indirectly tether cholesterol and sphingolipid-enriched membrane microdomains to the cytoskeleton. Caveolins possess a unique scaffolding domain that anchors receptors, ion channels, second messenger producing enzymes, and effector kinases, thereby sequestering them to caveolae, and modulating cellular signaling and vesicular transport. The lungs express numerous caveolae and high levels of caveolins; therefore they likely play an important role in lung physiology. Indeed, recent and ongoing studies indicate important roles for caveolae and caveolins in the airway epithelium, airway smooth muscle, airway fibroblasts, airway inflammatory cells and the pulmonary vasculature. We review the role of caveolae and caveolins in lung cells and discuss their involvement in cellular signaling associated with asthma, COPD, lung cancer, idiopathic pulmonary fibrosis and pulmonary vascular defects.

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

“…In this regard, it appears that caveolae may differentially modulate ASM responses to cytokines such as TNF-␣ vs. IL-13, at least in part due to caveolar vs. noncaveolar expression of their respective receptors (265). In contrast to these [Ca 2ϩ ] i /contraction data, reduced caveolin-1 expression has been reported to facilitate ASM proliferation (89,91,93). Thus it could be reasoned that caveolin-1 contributes to the balance between contractile vs. proliferative phenotype of ASM in the context of inflammation but in either fashion enhance airway changes in asthma for example.…”

“…Furthermore, signaling mechanisms within ASM itself could be involved. For example, caveolin-1 can inhibit proliferation (7,89,92), whereas the SOCE mechanisms STIM1 and Orai1 can enhance TGF-␤1-induced proliferation (79) (Fig. 5).…”

Caveolin-1 and force regulation in porcine airway smooth muscle

“…caveolae; lung; inflammation; cytokine; MAP kinase; RhoA; small interfering RNA CAVEOLAE, FLASK-SHAPED PLASMA membrane invaginations rich in cholesterol and sphingolipids, express any of three caveolin proteins (caveolin-1, caveolin-2, and/or caveolin-3). By virtue of caveolar expression of agonist receptors, ion channels, and other membrane proteins, as well as the association of caveolins with intracellular proteins, the role of caveolins as organizers and facilitators of signal transduction is now well recognized (12,23,38,62,67,81,82).Multiple studies including our own (16,28,33,61,68,73), have now demonstrated the presence of caveolae and caveolins in airway smooth muscle (ASM …”

“…Multiple studies including our own (16,28,33,61,68,73), have now demonstrated the presence of caveolae and caveolins in airway smooth muscle (ASM …”

Antenatal glucocorticoids counteract LPS changes in TGF-β pathway and caveolin-1 in ovine fetal lung

“…Cav-1 regulates the contractile phenotype of maturing airway smooth muscle cells under influence of TGF-␤1 (15). Altered expression of Cav-1 has been implicated in the pathogenesis of several lung diseases (14). Cav Ϫ/Ϫ mice have thickened alveolar walls and irregular alveolar spaces with increased deposition of extracellular matrix and TGF-␤ activity, whereas overexpression of Cav-1 aggravates lipopolysaccharide (LPS)-induced inflammation and subsequent lung injury (17,29).…”