High-fidelity fast excitatory neurotransmission in the mammalian central nervous system is conducted by the AMPA receptor (AMPAR) subfamily of ionotropic glutamate receptors. AMPARs exist as complexes of the pore-lining α subunits GluA1-4 and a number of auxiliary subunits shaping their functional properties. The first discovered family of auxiliary subunits comprises the transmembrane AMPAR regulatory proteins (TARPs). Together with germ cell-specific gene 1-like (GSG1L), they belong to the PMP-22/EMP/MP20/claudin superfamily sharing substantial sequence homology and a 4-transmembrane domain (4-TMD) topology. Here, we identify the claudin Cldn24 as a novel AMPAR auxiliary subunit in cerebellar granule cells (CGCs). Specifically accelerating the recovery of desensitized receptors, Cldn24 counterbalances gating modulation of GluA by TARP-γ2 and GSG1L in CGCs and hence enables fast reactivation of native receptors. These features substantially expand the tuning properties of hitherto known AMPAR auxiliary subunits and render Cldn24 a powerful enhancer of AMPAR fidelity.
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Tobias Strasdeit
Ehsan Amin
Sebastian Obst
Science Advances
Columbia University
Emory University
Johannes Gutenberg University Mainz
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Strasdeit et al. (Fri,) studied this question.
www.synapsesocial.com/papers/69ada8b2bc08abd80d5bbde5 — DOI: https://doi.org/10.1126/sciadv.aeb0196
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