English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein coupling.

Grünewald, S., Schupp, B., Ikeda, S. R., Kuner, R., Steigerwald, F., Kornau, H. C., et al. (2002). Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein coupling. Molecular Pharmacology, 61(5), 1070-1080. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11961124.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein coupling.

Files

show Files
hide Files
:
MolPharmacol_61_2002_1070.pdf (Any fulltext), 748KB
 
File Permalink:
-
Name:
MolPharmacol_61_2002_1070.pdf
Description:
-
OA-Status:
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-
OA-Status:
Locator:
http://dx.doi.org/10.1124/mol.61.5.1070 (Any fulltext)
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Grünewald, Sylvia, Author
Schupp, Bettina1, Author           
Ikeda, Stephen R., Author
Kuner, Rohini, Author
Steigerwald, Frank1, Author           
Kornau, Hans Christian1, Author           
Köhr, Georg1, Author           
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

Content

show
hide
Free keywords: -
 Abstract: Functional gamma-aminobutyric acid(B) (GABA(B)) receptors assemble from two subunits, GABA(B(1)) and GABA(B(2).) This heteromerization, which involves a C-terminal coiled-coil interaction, ensures efficient surface trafficking and agonist-dependent G-protein activation. In the present study, we took a closer look at the implications of the intracellular C termini of GABA(B(1)) and GABA(B(2)) for G-protein coupling. We generated a series of C-terminal mutants of GABA(B(1)) and GABA(B(2)) and tested them for physical interaction, surface trafficking, coupling to adenylyl cyclase, and G-protein-gated inwardly rectifying potassium channels in human embryonic kidney (HEK) 293 cells as well as on endogenous calcium channels in sympathetic neurons of the superior cervical ganglion (SCG). We found that the C-terminal interaction contributes only partly to the heterodimeric assembly of the subunits, indicating the presence of an additional interaction site. The described endoplasmic reticulum retention signal within the C terminus of GABA(B(1)) functioned only in the context of specific amino acids, which constitute part of the GABA(B(1)) coiled-coil sequence. This finding may provide a link between the retention signal and its shielding by the coiled coil of GABA(B(2).) In HEK293 cells, we observed that the two well-known GABA(B) receptor antagonists [S-(R*,R*)]-[3-[[1-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxypropyl](cyclohexylmethyl) phosphinic acid (CGP54626) and (+)-(2S)-5,5-dimethyl-2-morpholineacetic acid (SCH50911) CGP54626 and SCH50911 function as inverse agonists. The C termini of GABA(B(1)) and GABA(B(2)) strongly influenced agonist-independent G-protein coupling, although they were not necessary for agonist-dependent G-protein coupling. The C-terminal GABA(B) receptor mutants described here demonstrate that the active receptor conformation is stabilized by the coiled-coil interaction. Thus, the C-terminal conformation of the GABA(B) receptor may determine its constitutive activity, which could be a therapeutic target for inverse agonists.

Details

show
hide
Language(s): eng - English
 Dates: 2001-11-092002-01-252002-05-012002-05-01
 Publication Status: Issued
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Molecular Pharmacology
  Other : Mol. Pharmacol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Bethesda, Md. : American Society for Pharmacology and Experimental Therapeutics
Pages: - Volume / Issue: 61 (5) Sequence Number: - Start / End Page: 1070 - 1080 Identifier: ISSN: 0026-895X
CoNE: https://pure.mpg.de/cone/journals/resource/954925426203