Linked Life Data

17483093

Source:http://linkedlifedata.com/resource/pubmed/id/17483093

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2007-6-25
pubmed:abstractText
The subunit GluR2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subfamily of ionotropic glutamate receptors (GluRs) features a single amino acid at the narrow constriction of the pore loop that is altered from glutamine to arginine by RNA editing. This so-called Q/R site has been shown to play an important role in the determination of the electrophysiological properties of AMPA receptor complexes as well as of trafficking to the plasma membrane. The protein stargazin has also been shown to modulate electrophysiological properties and trafficking to the plasma membrane of AMPA receptors. In this study we examined via a series of mutants of the Q/R site of the AMPA receptor GluR1 whether the amino acid at this position has any influence on the modulatory effects mediated by stargazin. To this end, we analyzed current responses of Q/R site mutants upon application of glutamate and kainate and determined the amount of mutant receptor protein in the plasma membrane in Xenopus oocytes. Desensitization kinetics of several mutants were analyzed in HEK293 cells. We found that the stargazin-mediated decrease in receptor desensitization, the slowing of desensitization kinetics, and the kainate efficacy were all dependent on the amino acid at the Q/R site, whereas the stargazin-mediated increase in trafficking toward the plasma membrane remained independent of this amino acid. We propose that the Q/R site modulates the interaction of stargazin with the transmembrane domains of AMPA receptors via an allosteric mechanism and that this modulation leads to the observed differences in the electrophysiological properties of the receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18758-66
pubmed:meshHeading
pubmed-meshheading:17483093-Allosteric Site, pubmed-meshheading:17483093-Animals, pubmed-meshheading:17483093-Calcium Channels, pubmed-meshheading:17483093-Cell Line, pubmed-meshheading:17483093-Cell Membrane, pubmed-meshheading:17483093-Excitatory Amino Acid Agonists, pubmed-meshheading:17483093-Glutamic Acid, pubmed-meshheading:17483093-Humans, pubmed-meshheading:17483093-Ion Channel Gating, pubmed-meshheading:17483093-Kainic Acid, pubmed-meshheading:17483093-Kidney, pubmed-meshheading:17483093-Kinetics, pubmed-meshheading:17483093-Membrane Potentials, pubmed-meshheading:17483093-Mutagenesis, Site-Directed, pubmed-meshheading:17483093-Oocytes, pubmed-meshheading:17483093-Patch-Clamp Techniques, pubmed-meshheading:17483093-Protein Structure, Tertiary, pubmed-meshheading:17483093-Receptors, AMPA, pubmed-meshheading:17483093-Xenopus laevis
pubmed:year
2007
pubmed:articleTitle
Stargazin interaction with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors is critically dependent on the amino acid at the narrow constriction of the ion channel.
pubmed:affiliation
Department of Biochemistry I-Receptor Biochemistry, Ruhr University Bochum, D-44780 Bochum, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't