PMID- 10536013
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - Postsynaptic clustering of gamma-aminobutyric acid type A receptors by the gamma3
      subunit in vivo.
PG  - 12860-5
AB  - Synaptic localization of gamma-aminobutyric acid type A (GABA(A)) receptors is a 
      prerequisite for synaptic inhibitory function, but the mechanism by which
      different receptor subtypes are localized to postsynaptic sites is poorly
      understood. The gamma2 subunit and the postsynaptic clustering protein gephyrin
      are required for synaptic localization and function of major GABA(A) receptor
      subtypes. We now show that transgenic overexpression of the gamma3 subunit in
      gamma2 subunit-deficient mice restores benzodiazepine binding sites,
      benzodiazepine-modulated whole cell currents, and postsynaptic miniature
      currents, suggesting the formation of functional, postsynaptic receptors.
      Moreover, the gamma3 subunit can substitute for gamma2 in the formation of
      GABA(A) receptors that are synaptically clustered and colocalized with gephyrin
      in vivo. These clusters were formed even in brain regions devoid of endogenous
      gamma3 subunit, indicating that the factors present for clustering of gamma2
      subunit-containing receptors are sufficient to cluster gamma3 subunit-containing 
      receptors. The GABA(A) receptor and gephyrin-clustering properties of the ectopic
      gamma3 subunit were also observed for the endogenous gamma3 subunit, but only in 
      the absence of the gamma2 subunit, suggesting that the gamma3 subunit is at a
      competitive disadvantage with the gamma2 subunit for clustering of postsynaptic
      GABA(A) receptors in wild-type mice.
FAU - Baer, K
AU  - Baer K
AD  - Institute of Pharmacology, University of Zurich, Winterthurerstrasse 190, 8057
      Zurich, Switzerland.
FAU - Essrich, C
AU  - Essrich C
FAU - Benson, J A
AU  - Benson JA
FAU - Benke, D
AU  - Benke D
FAU - Bluethmann, H
AU  - Bluethmann H
FAU - Fritschy, J M
AU  - Fritschy JM
FAU - Luscher, B
AU  - Luscher B
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - 0 (Receptors, GABA-A)
RN  - 12794-10-4 (Benzodiazepines)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Benzodiazepines/metabolism
MH  - Binding Sites
MH  - DNA Primers
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Receptors, GABA-A/chemistry/*metabolism
MH  - Synapses/*metabolism
PMC - PMC23133
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12860 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12860-5. doi:
      10.1073/pnas.96.22.12860.