Document Detail


Involvement of cholesterol in synaptic vesicle swelling.
MedLine Citation:
PMID:  20407079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies demonstrate that cholesterol plays a critical role in the regulation of neurotransmitter release and that secretory vesicle swelling is a requirement for the regulated expulsion of intravesicular contents during cell secretion. In view of this, the involvement of cholesterol in synaptic vesicle swelling was hypothesized and tested in the present study, using isolated synaptic vesicles from rat brain and the determination of their swelling competency in the presence and absence of cholesterol. The involvement of the water channel aquaporin-6 (AQP-6) and proton pump vH(+)-ATPase in GTP-G(alpha o)-mediated synaptic vesicle swelling has been reported previously. Mastoparan, the amphiphilic tetradecapeptide from wasp venom, known to activate the GTPase activity of G(alpha o/i) proteins, stimulates synaptic vesicle swelling in the presence of GTP. In the current study, using nanometer-scale precision measurements of isolated synaptic vesicles, we report for the first time that depletion of cholesterol from synaptic vesicle membrane results in a significant loss of GTP-mastoparan-stimulable synaptic vesicle swelling. In contrast, incorporation of cholesterol into the synaptic vesicle membrane potentiates GTP-mastoparan-stimulable vesicle swelling. Our study further demonstrates that this effect of cholesterol is due, in part, to its involvement in the interactions between AQP-6, vH(+)-ATPase and the GTP-binding G(alpha o) protein at the synaptic vesicle membrane.
Authors:
Jin-Sook Lee; Won Jin Cho; Leah Shin; Bhanu P Jena
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  235     ISSN:  1535-3699     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-04-28     Revised Date:  2010-07-29    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  England    
Other Details:
Languages:  eng     Pagination:  470-7     Citation Subset:  IM    
Affiliation:
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aquaporin 6 / metabolism
Brain / cytology,  metabolism
Cholesterol / metabolism*
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Guanosine Triphosphate / metabolism
Microscopy, Atomic Force
Peptides / pharmacology
Proton-Translocating ATPases / metabolism
Rats
Rats, Sprague-Dawley
Synaptic Vesicles / drug effects,  metabolism*,  ultrastructure
Wasp Venoms / pharmacology
Grant Support
ID/Acronym/Agency:
NS39918/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Aquaporin 6; 0/Peptides; 0/Wasp Venoms; 57-88-5/Cholesterol; 72093-21-1/mastoparan; 86-01-1/Guanosine Triphosphate; EC 3.6.3.14/Proton-Translocating ATPases; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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