The ins and outs of caveolar signaling. m2 muscarinic cholinergic receptors and eNOS activation versus neuregulin and ErbB4 signaling in cardiac myocytes

Olivier Feron, You Yang Zhao, Ralph A. Kelly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Endothelial cells constitutively express the NOS isoform eNOS, which generates NO in response to specific extracellular signals to regulate vascular smooth muscle tone, vascular permeability, and platelet adhesion, among other actions. In addition to coronary vascular and endocardial endothelium, both atrial and ventricular myocytes express eNOS, the activation of which is also dependent on specific intracellular and extracellular signals. eNOS is targeted in cardiac myocytes to caveolae in plasma membranes and, in the case of cardiac myocytes, possibly T-tubular membranes as well. eNOS targeting to caveolae in cardiac myocytes requires co-translational myristoylation and subsequent palmitoylation for efficient targeting of the enzyme to the specialized lipid microdomains characteristic of caveolae. Although eNOS also contains a caveolin binding motif, this is insufficient for correct targeting of eNOS to caveolae. Recent evidence obtained from ventricular myocytes of mice with targeted disruption of the eNOS gene indicates that the lack of functional eNOS interrupts muscarinic cholinergic control of I(Ca-L) in these cells, eNOS-/- mice are hypertensive and develop cardiac hypertrophy as they age, and these animals also exhibit an accelerated degree of vascular remodeling in response to injury. Reconstitution experiments confirm both the essential role of eNOS in coupling m2 AchR signaling to the control of I(Ca-L) and myocyte automaticity and the importance of eNOS subcellular localization within caveolae in mediating this signal transduction pathway. It appears that translocation into caveolae is essential for signaling. However, this is not the case with all receptors associated with caveolae.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume874
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Fingerprint Dive into the research topics of 'The ins and outs of caveolar signaling. m2 muscarinic cholinergic receptors and eNOS activation versus neuregulin and ErbB4 signaling in cardiac myocytes'. Together they form a unique fingerprint.

Cite this