Journal article
Selective localization of collybistin at a subset of inhibitory synapses in brain circuits
Journal of Comparative Neurology, Vol.520(1), pp.130-141
2012
Abstract
Collybistin is a brain-specific guanine nucleotide exchange factor (GEF) that is crucial for the postsynaptic accumulation of gephyrin and γ-aminobutyric acid A receptors (GABAARs) 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 by 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 GABAARs 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 co-localization values in different brain regions. Moreover, collybistin co-localizes with GABAARs containing the α1, α2, or α3 subunits, arguing against a selective association with specific GABAAR 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. © 2011 Wiley Periodicals, Inc.
Details
- Title
- Selective localization of collybistin at a subset of inhibitory synapses in brain circuits
- Authors
- A Patrizi (Author) - National Institute of Neuroscience, ItalyL Viltono (Author) - National Institute of Neuroscience, ItalyE Frola (Author) - National Institute of Neuroscience, ItalyK Harvey (Author) - University College London, United KingdomRobert J Harvey (Author) - University College London, United KingdomM Sassoè-Pognetto (Author) - National Institute of Neuroscience, Italy
- Publication details
- Journal of Comparative Neurology, Vol.520(1), pp.130-141
- Publisher
- John Wiley & Sons Inc.
- Date published
- 2012
- DOI
- 10.1002/cne.22702
- ISSN
- 0021-9967
- Copyright note
- Copyright © 2012 the authors. This is the accepted version of the following article: Patrizi, A; Viltono, L; Frola, E; Harvey, K; Harvey, Robert J; Sassoè-Pognetto, M (2012) Selective localization of collybistin at a subset of inhibitory synapses in brain circuits. Journal of Comparative Neurology. 520:1 pp.130-141, which has been published in final form at http://dx.doi.org/10.1002/cne.22702
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99451095302621
- Output Type
- Journal article
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