The Epac-Rap1 signaling pathway controls cAMP-mediated exocytosis of Weibel-Palade bodies in endothelial cells

37Citations
Citations of this article
47Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Endothelial cells contain specialized storage organelles called Weibel-Palade bodies (WPBs) that release their content into the vascular lumen in response to specific agonists that raise intracellular Ca2+ or cAMP. We have previously shown that cAMP-mediated WPB release is dependent on protein kinase A (PKA) and involves activation of the small GTPase RalA. Here, we have investigated a possible role for another PKA-independent cAMP-mediated signaling pathway in the regulation of WPB exocytosis, namely the guanine nucleotide exchange factor Epac1 and its substrate, the small GTPase Rap1. Epinephrine stimulation of endothelial cells leads to Rap1 activation in a PKA-independent fashion. siRNA-mediated knockdown of Epac1 abolished epinephrine-induced activation of Rap1 and resulted in decreased epinephrine-induced WPB exocytosis. Down-regulation of Rap1 expression and prevention of Rap1 activation through overexpression of Rap1GAP effectively reduced epinephrine- but not thrombin-induced WPB exocytosis. Taken together, these data uncover a new Epac-Rap1-dependent pathway by which endothelial cells can regulate WPB exocytosis in response to agonists that signal through cAMP. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Van Hooren, K. W. E. M., Van Agtmaal, E. L., Fernandez-Borja, M., Van Mourik, J. A., Voorberg, J., & Bierings, R. (2012). The Epac-Rap1 signaling pathway controls cAMP-mediated exocytosis of Weibel-Palade bodies in endothelial cells. Journal of Biological Chemistry, 287(29), 24713–24720. https://doi.org/10.1074/jbc.M111.321976

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 18

55%

Researcher 10

30%

Professor / Associate Prof. 3

9%

Lecturer / Post doc 2

6%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 17

45%

Biochemistry, Genetics and Molecular Bi... 13

34%

Medicine and Dentistry 6

16%

Neuroscience 2

5%

Save time finding and organizing research with Mendeley

Sign up for free