Document Detail

Caveolin-1 regulates the delivery and endocytosis of the glutamate transporter, excitatory amino acid carrier 1.
MedLine Citation:
PMID:  17715130     Owner:  NLM     Status:  MEDLINE    
The sodium-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1), has been implicated in the regulation of excitatory signaling and prevention of cell death in the nervous system. There is evidence that EAAC1 constitutively cycles on and off the plasma membrane and that under steady state conditions up to 80% of the transporter is intracellular. As is observed with other neurotransmitter transporters, the activity of EAAC1 is regulated by a variety of molecules, and some of these effects are associated with redistribution of EAAC1 on and off the plasma membrane. In the present study we tested the hypothesis that a structural component of lipid rafts, caveolin-1 (Cav-1), may participate in EAAC1 trafficking. Using C6 glioma cells as a model system, co-expression of Cav-1 S80E (a dominant-negative variant) or small interfering RNA-mediated knock-down of caveolin-1 reduced cell surface expression of myc epitope-tagged EAAC1 or endogenous EAAC1, respectively. Cav-1 S80E slowed the constitutive delivery and endocytosis of myc-EAAC1. In primary cultures derived from caveolin-1 knock-out mice, a similar reduction in delivery and internalization of endogenous EAAC1 was observed. We also found that caveolin-1, caveolin-2, or Cav-1 S80E formed immunoprecipitable complexes with EAAC1 in C6 glioma and/or transfected HEK cells. Together, these data provide strong evidence that caveolin-1 contributes to the trafficking of EAAC1 on and off the plasma membrane and that these effects are associated with formation of EAAC1-caveolin complexes.
Marco I González; Elizabeth Krizman-Genda; Michael B Robinson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-08-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29855-65     Citation Subset:  IM    
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104-4318, USA.
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MeSH Terms
Amino Acid Transport System X-AG / metabolism*
Astrocytes / metabolism
Caveolin 1 / biosynthesis*,  physiology*
Cell Line, Tumor
Cell Membrane / metabolism
Excitatory Amino Acid Transporter 3 / metabolism*
Membrane Microdomains / metabolism
Mice, Knockout
Neurotransmitter Agents / metabolism
Grant Support
Reg. No./Substance:
0/Amino Acid Transport System X-AG; 0/Caveolin 1; 0/Excitatory Amino Acid Transporter 3; 0/Neurotransmitter Agents; 0/Slc1a1 protein, mouse; 0/Slc1a1 protein, rat

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