spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 29 April 2008
doi: 10.1242/jcs.020958

Journal of Cell Science 121, 1704-1717 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.020958v1
121/10/1704    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Waldeck-Weiermair, M.
Right arrow Articles by Graier, W. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Waldeck-Weiermair, M.
Right arrow Articles by Graier, W. F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression

Markus Waldeck-Weiermair1,*, Cristina Zoratti1,*, Karin Osibow1, Nariman Balenga2, Edith Goessnitzer3, Maria Waldhoer2, Roland Malli1 and Wolfgang F. Graier1,*,{ddagger}

1 Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, A8010, Austria
2 Institute of Experimental and Clinical Pharmacology, Medical University Graz, Graz, A8010, Austria
3 Institute of Pharmaceutical Chemistry, University Graz, Graz Austria

{ddagger} Author for correspondence (e-mail: wolfgang.graier{at}meduni-graz.at)

Accepted 17 February 2008

Although the endocannabinoid anandamide is frequently described to act predominantly in the cardiovascular system, the molecular mechanisms of its signaling remained unclear. In human endothelial cells, two receptors for anandamide were found, which were characterized as cannabinoid 1 receptor (CB1R; CNR1) and G-protein-coupled receptor 55 (GPR55). Both receptors trigger distinct signaling pathways. It crucially depends on the activation status of integrins which signaling cascade becomes promoted upon anandamide stimulation. Under conditions of inactive integrins, anandamide initiates CB1R-derived signaling, including Gi-protein-mediated activation of spleen tyrosine kinase (Syk), resulting in NF{kappa}B translocation. Furthermore, Syk inhibits phosphoinositide 3-kinase (PI3K) that represents a key protein in the transduction of GPR55-originated signaling. However, once integrins are clustered, CB1R splits from integrins and, thus, Syk cannot further inhibit GPR55-triggered signaling resulting in intracellular Ca2+ mobilization from the endoplasmic reticulum (ER) via a PI3K-Bmx-phospholipase C (PLC) pathway and activation of nuclear factor of activated T-cells. Altogether, these data demonstrate that the physiological effects of anandamide on endothelial cells depend on the status of integrin clustering.

Key words: Anandamide, Bmx/Etk, Cannabinoid signaling, CB1 receptor, GPR55, Ca2+ signaling, Integrins, Syk


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J Mol EndocrinolHome page
G. Turu and L. Hunyady
Signal transduction of the CB1 cannabinoid receptor
J. Mol. Endocrinol., February 1, 2010; 44(2): 75 - 85.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. S. Whyte, E. Ryberg, N. A. Sims, S. A. Ridge, K. Mackie, P. J. Greasley, R. A. Ross, and M. J. Rogers
The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo
PNAS, September 22, 2009; 106(38): 16511 - 16516.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. M. Henstridge, N. A. B. Balenga, L. A. Ford, R. A. Ross, M. Waldhoer, and A. J. Irving
The GPR55 ligand L-{alpha}-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation
FASEB J, January 1, 2009; 23(1): 183 - 193.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
S. Oka, T. Toshida, K. Maruyama, K. Nakajima, A. Yamashita, and T. Sugiura
2-Arachidonoyl-sn-glycero-3-phosphoinositol: A Possible Natural Ligand for GPR55
J. Biochem., January 1, 2009; 145(1): 13 - 20.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2008