Pituitary adenylate cyclase-activating polypeptide induces translocation of its G-protein-coupled receptor into caveolin-enriched membrane microdomains, leading to enhanced cyclic AMP generation and neurite outgrowth in PC12 cells

Zhang, Weishi, Duan, Wei, Cheung, Nam Sang, Huang, Zhili, Shao, Ke and Li, Qiu-Tian 2007, Pituitary adenylate cyclase-activating polypeptide induces translocation of its G-protein-coupled receptor into caveolin-enriched membrane microdomains, leading to enhanced cyclic AMP generation and neurite outgrowth in PC12 cells, Journal of neurochemistry, vol. 103, no. 3, pp. 1157-1167.


Title Pituitary adenylate cyclase-activating polypeptide induces translocation of its G-protein-coupled receptor into caveolin-enriched membrane microdomains, leading to enhanced cyclic AMP generation and neurite outgrowth in PC12 cells
Author(s) Zhang, Weishi
Duan, Wei
Cheung, Nam Sang
Huang, Zhili
Shao, Ke
Li, Qiu-Tian
Journal name Journal of neurochemistry
Volume number 103
Issue number 3
Start page 1157
End page 1167
Publisher Wiley-Blackwell Publishing Ltd
Place of publication Chichester, England
Publication date 2007-07-11
ISSN 0022-3042
1471-4159
Keyword(s) cyclic AMP
lipid rafts/caveolae
neurite outgrowth
pituitary adenylate cyclase-activating polypeptide • pituitary adenylate cyclase-activating polypeptide receptors
signal transduction
Summary Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin/glucagon/vasoactive intestinal peptide family expressed throughout the nervous system, binds to the PACAP-specific G-protein-coupled receptor family members to promote both neuronal differentiation and survival. Although the PACAP receptor is known to activate its effector protein, adenylate cyclase (AC), and thus enhance cAMP generation, the molecular mechanism utilized by the receptor to activate AC is lacking. Here, we show that PACAP induces neurite outgrowth in PC12 cells by induction of translocation of the PACAP type 1 receptor (PAC1R) into caveolin-enriched Triton X-100-insoluble microdomains, leading to stronger PAC1R-AC interaction and elevated cAMP production. Moreover, we demonstrate that translocation of PAC1R is blocked by various treatments that selectively disrupt caveolae. As a result, intracellular cAMP level is decreased and consequently the PACAP-induced neurite outgrowth retarded. In contrast, addition of exogenous ganglioside GM1 to the cells shows the opposite effects. These results therefore identify the PACAP-induced translocation of its G-protein-coupled receptor into caveolae, where both AC and the regulating G-proteins reside, as the key molecular event in activating AC and inducing cAMP-mediated differentiation of PC12 cells.
Language eng
Field of Research 110104 Medical Biochemistry: Lipids
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007438

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in TR Web of Science
Scopus Citation Count Cited 11 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 406 Abstract Views  -  Detailed Statistics
Created: Mon, 29 Sep 2008, 08:52:07 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.