Collybistin SH3-protein isoforms are expressed in the rat brain promoting gephyrin and GABA-A receptor clustering at GABAergic synapses.

Autor: George S; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Bear J Jr; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Taylor MJ; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Kanamalla K; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Fekete CD; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Chiou TT; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Miralles CP; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA., Papadopoulos T; Department of Molecular Biology, Universitätsmedizin Göttingen, Göttingen, Germany., De Blas AL; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2021 May; Vol. 157 (4), pp. 1032-1051. Date of Electronic Publication: 2021 Jan 05.
DOI: 10.1111/jnc.15270
Abstrakt: Collybistin (CB) is a guanine nucleotide exchange factor (GEF) selectively localized at GABAergic and glycinergic postsynapses. Analysis of mRNA shows that several isoforms of collybistin are expressed in the brain. Some of the isoforms have a SH3 domain (CBSH3+) and some have no SH3 domain (CBSH3-). The CBSH3+ mRNAs are predominantly expressed over CBSH3-. However, in an immunoblot study of mouse brain homogenates, only CBSH3+ protein isoforms were detected, proposing that CBSH3- protein might not be expressed in the brain. The expression or lack of expression of CBSH3- protein is an important issue because CBSH3- has a strong effect in promoting the postsynaptic clustering of gephyrin and GABA-A receptors (GABA A Rs). Moreover CBSH3- is constitutively active; therefore lower expression of CBSH3- protein might play a relatively stronger functional role than the more abundant but self-inhibited CBSH3+ isoforms, which need to be activated. We are now showing that: (a) CBSH3- protein is expressed in the brain; (b) parvalbumin positive (PV+) interneurons show higher expression of CBSH3- protein than other neurons; (c) CBSH3- is associated with GABAergic synapses in various regions of the brain and (d) knocking down CBSH3- in hippocampal neurons decreases the synaptic clustering of gephyrin and GABA A Rs. The results show that CBSH3- protein is expressed in the brain and that it plays a significant role in the size regulation of the GABAergic postsynapse.
(© 2020 International Society for Neurochemistry.)
Databáze: MEDLINE
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