Abstract:
:Most G protein-coupled receptors contain a conserved pair of extracellular cysteine residues that are predicted to form a disulfide bond linking the first and second extracellular loops. Previous studies have shown that this disulfide bond may be critical for ligand binding, receptor activation, and/or proper receptor folding. However, the potential importance of the two conserved cysteine residues for proper receptor cell surface localization has not been investigated systematically. To address this issue, we used the rat M3 muscarinic receptor as a model system. Most studies were carried out with a modified version of this receptor subtype (lacking potential N-glycosylation sites and the central portion of the third intracellular loop) that could be readily detected via western blot analysis. Cys-->Ala mutant receptors were generated, transiently expressed in COS-7 cells, and then examined for their subcellular distribution and functional properties. ELISA and immunofluorescence studies showed that the presence of both conserved cysteine residues (corresponding to C140 and C220 in the rat M3 muscarinic receptor sequence) is required for efficient expression of the M3 muscarinic receptor on the cell surface. On the other hand, these residues were found not to be essential for protein stability (determined via immunoblotting) and receptor-mediated G protein activation (studied in second messenger assays). These results shed new light on the functional role of the two extracellular cysteine residues present in most G protein-coupled receptors.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Zeng FY,Soldner A,Schöneberg T,Wess Jdoi
10.1046/j.1471-4159.1999.0722404.xkeywords:
subject
Has Abstractpub_date
1999-06-01 00:00:00pages
2404-14issue
6eissn
0022-3042issn
1471-4159journal_volume
72pub_type
杂志文章abstract::Acute seizures and other stimuli that increase neuronal activity cause a rapid induction of the immediate-early genes c-fos and c-jun, also referred to as nuclear proto-oncogenes, in the nervous system. In the present study, rats were administered one or more electroconvulsive seizures (ECS) and the responsiveness of ...
journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:1981-03-01 00:00:00
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更新日期:1992-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07347.x
更新日期:2011-11-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1982-06-01 00:00:00
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更新日期:2007-09-01 00:00:00
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:2000-04-01 00:00:00
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:1982-04-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:1995-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2008-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2004-05-01 00:00:00
abstract::Previous studies showed that prolonged access to cocaine or heroin self-administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacok...
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更新日期:2003-07-01 00:00:00