Collybistin is required for both the formation and maintenance of GABAergic postsynapses in the hippocampus.
Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor, which interacts with the inhibitory receptor anchoring protein gephyrin. In the hippocampus of constitutively Cb-deficient adult mice, gephyrin and gephyrin-dependent GABA(A) receptors (GABA(A)Rs) are lost from postsynaptic sites. Here, we used a Cre-loxP system to inactivate the Cb gene in the forebrain at different developmental stages. Deletion of Cb during embryonic development prevented gephyrin clustering during synaptogenesis and caused an accumulation of gephyrin aggregates in the cell body of CA1 pyramidal neurons. Inactivation of the Cb gene during the third postnatal week resulted in a protracted loss of postsynaptic gephyrin clusters and the appearance of cytoplasmic gephyrin aggregates. These changes in gephyrin distribution were accompanied by a similar reduction in synaptically localized GABA(A)R gamma2-subunit immunoreactivity. Our data show that Cb is required for both the initial localization and maintenance of gephyrin and gephyrin-dependent GABA(A)Rs at inhibitory postsynaptic membrane specializations in the hippocampus.
Papadopoulos
Theofilos
T
Department of Neurochemistry, Max-Planck Institute for Brain Research, Frankfurt am Main, Germany.
Eulenburg
Volker
V
Reddy-Alla
Suneel
S
Mansuy
Isabelle M
IM
Li
Yuqing
Y
Betz
Heinrich
H
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000254:growth & development / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C546280:Gabrg2 protein, mouse; C073441:gephyrin