+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

The GABA(B2) subunit is critical for the trafficking and function of native GABA(B) receptors

The GABA(B2) subunit is critical for the trafficking and function of native GABA(B) receptors

Biochemical Pharmacology 68(8): 1655-1666

Studies in heterologous systems have demonstrated that heterodimerisation of the two GABA(B) receptor subunits appears to be crucial for the trafficking and signalling of the receptor. Gene targeting of the GABA(B1) gene has demonstrated that the expression of GABA(B1) is essential for GABA(B) receptor function in the central nervous system (CNS). However, the contribution of the GABA(B2) subunit in the formation of native GABA(B) receptors is still unclear, in particular whether other proteins can substitute for this subunit. We have created a transgenic mouse in which the endogenous GABA(B2) gene has been mutated in order to express a C-terminally truncated version of the protein. As a result, the GABA(B1) subunit does not reach the cell surface and concomitantly both pre- and post-synaptic GABA(B) receptor functions are abolished. Taken together with previous gene deletion studies for the GABA(B1) subunit, this suggests that classical GABA(B) function in the brain is exclusively mediated by GABA(B1/2) heteromers.

(PDF emailed within 0-6 h: $19.90)

Accession: 012629368

Download citation: RISBibTeXText

PMID: 15451409

DOI: 10.1016/j.bcp.2004.07.032

Related references

gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505(1): 18-31, 2007

Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit. Molecular Pharmacology 57(3): 419-426, 2000

Role of the GABA(A)beta2, GABA(A)alpha6, GABA(A)alpha1 and GABA(A)gamma2 receptor subunit genes cluster in drug responses and the development of alcohol dependence. Neurochemistry International 37(5-6): 413-423, 2000

Subunit-specific trafficking of GABA(A) receptors during status epilepticus. Journal of Neuroscience 28(10): 2527-2538, 2008

Expressed homo-oligomeric Drosophila melanogaster GABA receptors offer insights into the characteristic pharmacology of native insect GABA receptors. Journal of Physiology (Cambridge) 495P(0): 40P, 1996

Glutamic acid decarboxylases and GABA transporters determine GABA trafficking and function. Society for Neuroscience Abstracts 27(2): 1838, 2001

Subunit specific, activity dependent trafficking of GABA(A) receptors during status epilepticus. 2007

Efficacy and potency of GABA action in native and recombinant GABA-A receptors. Society for Neuroscience Abstracts 19(1-3): 851, 1993

Full and partial modulation of neurosteroids on GABA action in native and recombinant GABA-A receptors. Society for Neuroscience Abstracts 18(1-2): 402, 1992

Evaluation of native GABA(A) receptors containing an alpha 5 subunit. European Journal of Pharmacology 413(1): 63-72, 2001

Pentobarbital is a more efficacious agonist than GABA at GABA receptors containing the alpha4 subunit. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 571 8, 2003

Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABA(A) receptors. European Journal of Neuroscience 33(8): 1471-1482, 2011

Graded response to GABA by native extrasynaptic GABA receptors. Journal of Neurochemistry 97(5): 1349-1356, 2006

Kinetic and pharmacological properties of GABA(A) receptors in single thalamic neurons and GABA(A) subunit expression. Journal of Neurophysiology 86(5): 2312-2322, 2001

Perisynaptic Localization of Subunit-Containing Gaba A Receptors and Their Activation by Gaba Spillover in the Mouse Dentate Gyrus. The Journal of Neuroscience 23(33): 10650-10661, 2003