© 1999 American Heart Association, Inc.
Editorials |
Caveolar Microdomains of the Sarcolemma
Compartmentation of Signaling Molecules Comes of Age
From the Department of Pharmacology, University of California, San Diego, La Jolla Calif.
Correspondence to Paul A. Insel, MD, Department of Pharmacology 0636, University of California, San Diego, 9500 Gilman Dr MC0636, BSB 3076, La Jolla, CA 92093-0636. E-mail pinsel@ucsd.edu
Key Words: caveolae • G protein–coupled receptor • protein kinase C • extracellular signal-regulated protein kinase • clathrin-coated pit
For more than two decades, investigators who have been studying signal transduction in the heart (and other tissues) have struggled to explain data implicating the existence of "compartmentation." The data have included evidence for selective effects of certain types of hormonal and neurotransmitter agonists on "downstream" events, in spite of their utilization of common "upstream" second messenger pathways.1 2 The concept of compartmentation arose, at least partially, as an explanation for such phenomena. Yet progress in defining the physical nature of these compartments has, until recently, been rather slow. One problem has been that the biochemical paradigm, which typically involves destroying cells, isolating subcellular fractions, and assaying enzymatic or other activity, is not particularly well suited for precise identification of signaling domains responsible for compartmentation. Consider the folly of this type of approach if one were to use it to identify each of the parts of an appliance, such as a television set. One would smash the appliance, breaking it down into smaller pieces and then attempt to assemble these "fractions" in order to try and learn the function of each component.
Nevertheless, progress has recently accelerated in this area, in part
because of evolving notions regarding the existence of specialized
regions of the sarcolemmal membrane. Early work in a variety of cell
types focused on the role of clathrin-coated pit regions that were
involved in receptor-mediated endocytosis, in particular of transport
proteins and certain receptors.3 More recently, such
coated pit regions have been implicated in receptor-promoted
internalization of G protein–coupled
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