Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.

Autor: George S; Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, U-3156, Storrs, CT, 06269-3156, USA., Chiou TT; Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, U-3156, Storrs, CT, 06269-3156, USA., Kanamalla K; Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, U-3156, Storrs, CT, 06269-3156, USA., De Blas AL; Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, U-3156, Storrs, CT, 06269-3156, USA. angel.deblas@uconn.edu.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2022 Jul; Vol. 42 (5), pp. 1585-1604. Date of Electronic Publication: 2021 Feb 05.
DOI: 10.1007/s10571-021-01050-1
Abstrakt: It has been shown that subunit composition is the main determinant of the synaptic or extrasynaptic localization of GABA A receptors (GABA A Rs). Synaptic and extrasynaptic GABA A Rs are involved in phasic and tonic inhibition, respectively. It has been proposed that synaptic GABA A Rs bind to the postsynaptic gephyrin/collybistin (Geph/CB) lattice, but not the typically extrasynaptic GABA A Rs. Nevertheless, there are no studies of the direct binding of various types of GABA A Rs with the submembranous Geph/CB lattice in the absence of other synaptic proteins, some of which are known to interact with GABA A Rs. We have reconstituted GABA A Rs of various subunit compositions, together with the Geph/CB scaffold, in HEK293 cells, and have investigated the recruitment of surface GABA A Rs by submembranous Geph/CB clusters. Results show that the typically synaptic α1β3γ2 GABA A Rs were trapped by submembranous Geph/CB clusters. The α5β3γ2 GABA A Rs, which are both synaptic and extrasynaptic, were also trapped by Geph/CB clusters. Extrasynaptic α4β3δ GABA A Rs consistently showed little or no trapping by the Geph/CB clusters. However, the extrasynaptic α6β3δ, α1β3, α6β3 (and less α4β3) GABA A Rs were highly trapped by the Geph/CB clusters. AMPA and NMDA glutamate receptors were not trapped. The results suggest: (I) in the absence of other synaptic molecules, the Geph/CB lattice has the capacity to trap not only synaptic but also several typically extrasynaptic GABA A Rs; (II) the Geph/CB lattice is important but does not play a decisive role in the synaptic localization of GABA A Rs; and (III) in neurons there must be mechanisms preventing the trapping of several typically extrasynaptic GABA A Rs by the postsynaptic Geph/CB lattice.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)
Databáze: MEDLINE
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