Caveolae and lipid rafts: G protein-coupled receptor signaling microdomains in cardiac myocytes

A growing body of data indicates that multiple signal transduction events in the heart occur via plasma membrane receptors located in signaling microdomains. Lipid rafts, enriched in cholesterol and sphingolipids, form one such microdomain along with a subset of lipid rafts, caveolae, enriched in the protein caveolin. In the heart, a key caveolin is caveolin-3, whose scaffolding domain is thought to serve as an anchor for other proteins. In spite of the original morphologic definition of caveolae ("little caves"), most work related to their role in compartmenting signal transduction molecules has involved subcellular fractionation or immunoprecipitation with anti-caveolin antibodies. Use of such approaches has documented that several G protein-coupled receptors (GPCR), and their cognate heterotrimeric G proteins and effectors, localize to lipid rafts/caveolae in neonatal cardiac myocytes. Our recent findings support the view that adult cardiac myocytes appear to have different patterns of localization of such components compared to neonatal myocytes and cardiac fibroblasts. Such results imply the existence of multiple subcellular microdomains for GPCR-mediated signal transduction in cardiac myocytes, in particular adult myocytes, and raise a major unanswered question: what are the precise mechanism(s) that determine co-localization of GPCR and post-receptor components with lipid rafts/caveolae in cardiac myocytes and other cell types?