Selective localization of collybistin at a subset of inhibitory synapses in brain circuits.

Patrizi, A., Viltono, L., Frola, E., Harvey, K., Harvey, R.J. and Sassoè-Pognetto, M. (2011) Selective localization of collybistin at a subset of inhibitory synapses in brain circuits. Journal of Comparative Neurology . 10.1002/cne.22702.

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DOI: 10.1002/cne.22702

Abstract

Collybistin is a brain-specific guanine nucleotide exchange factor (GEF) that is crucial for the postsynaptic accumulation of gephyrin and GABA(A) Rs at a specific subset of inhibitory synapses. Our understanding of the in vivo function of collybistin has been hampered by lack of information about the synaptic localization of this protein in brain circuits. Here we describe the subcellular localization of endogenous collybistin using antibodies raised against distinct molecular domains that should recognize the majority of endogenous collybistin isoforms. We show that collybistin co-clusters with gephyrin and GABA(A) Rs in synaptic puncta and is recruited to postsynaptic specializations early during synapse development. Notably, collybistin is present in only a subset of gephyrin-positive synapses, with variable colocalization values in different brain regions. Moreover, collybistin colocalizes with GABA(A) Rs containing the α1, α2 or α3 subunits, arguing against a selective association with specific GABA(A) R subtypes. Surprisingly, we found that collybistin is expressed only transiently in Purkinje cells, suggesting that in these cerebellar neurons collybistin plays a selective role during the initial assembly of postsynaptic specializations. These data reveal a remarkable heterogeneity in the organization of GABAergic synapses and provide an anatomical basis for interpreting the variable effects caused by disruption of the collybistin gene in human X-linked intellectual disability and mouse knockout models. J. Comp. Neurol., 2011. © 2011 Wiley-Liss, Inc.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2296
Journal or Publication Title:Journal of Comparative Neurology
Deposited By:Library Staff
Deposited On:06 Oct 2011 11:23
Last Modified:06 Oct 2011 11:23

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