C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors

Pagano, A. and Rovelli, G. and Mosbacher, J. and Lohmann, T. and Duthey, B. and Stauffer, D. and Ristig, D. and Schuler, V. and Meigel, I. and Lampert, C. and Stein, T. and Prezeau, L. and Blahos, J. and Pin, J. and Froestl, W. and Kuhn, R. and Heid, J. and Kaupmann, K. and Bettler, B.. (2001) C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors. Journal of neuroscience, Vol. 21, H. 4. pp. 1189-1202.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5262265

Downloads: Statistics Overview


Assembly of fully functional GABA(B) receptors requires heteromerization of the GABA(B(1)) and GABA(B(2)) subunits. It is thought that GABA(B(1)) and GABA(B(2)) undergo coiled-coil dimerization in their cytoplasmic C termini and that assembly is necessary to overcome GABA(B(1)) retention in the endoplasmatic reticulum (ER). We investigated the mechanism underlying GABA(B(1)) trafficking to the cell surface. We identified a signal, RSRR, proximal to the coiled-coil domain of GABA(B(1)) that when deleted or mutagenized allows for surface delivery in the absence of GABA(B(2)). A similar motif, RXR, was recently shown to function as an ER retention/retrieval (ERR/R) signal in K(ATP) channels, demonstrating that G-protein-coupled receptors (GPCRs) and ion channels use common mechanisms to control surface trafficking. A C-terminal fragment of GABA(B(2)) is able to mask the RSRR signal and to direct the GABA(B(1)) monomer to the cell surface, where it is functionally inert. This indicates that in the heteromer, GABA(B(2)) participates in coupling to the G-protein. Mutagenesis of the C-terminal coiled-coil domains in GABA(B(1)) and GABA(B(2)) supports the possibility that their interaction is involved in shielding the ERR/R signal. However, assembly of heteromeric GABA(B) receptors is possible in the absence of the C-terminal domains, indicating that coiled-coil interaction is not necessary for function. Rather than guaranteeing heterodimerization, as previously assumed, the coiled-coil structure appears to be important for export of the receptor complex from the secretory apparatus.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

Repository Staff Only: item control page