Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo.
The ability of neurons to display more than a single GABA(A)-receptor subtype per cell requires intricate targeting mechanisms. Analysis by confocal laser scanning microscopy revealed that the alpha2- and alpha5-subunits differed strikingly in their subcellular distribution in hippocampal pyramidal cells and olfactory bulb granule cells, while the distribution of the gamma2-subunit was rather uniform. In mutant mice lacking the alpha5-subunit gene due to a chromosomal deletion, the absence of the alpha5-subunit was accompanied by a corresponding decrease of the gamma2-subunit immunoreactivity. In striking contrast, the subcellular distribution of the alpha2-subunit was unchanged in these mutant mice. These findings indicate that the assembly of distinct GABA(A)-receptor subtypes in the same neuron is regulated independently. Furthermore, the alpha-subunit is a prime candidate for providing domains which direct subcellular targeting.
Institute of Pharmacology, University of Zürich, Switzerland.
J M
JM
Fritschy
D K
DK
Johnson
H
H
Mohler
U
U
Rudolph
D000818:Animals; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D018034:Olfactory Receptor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D011963:Receptors, GABA-A