Journal
EMBO JOURNAL
Volume 25, Issue 5, Pages 987-999Publisher
WILEY
DOI: 10.1038/sj.emboj.7600995
Keywords
actin; extrasynaptic; GABA(A) receptor; radixin; alpha 5 subunit
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Neurotransmitter receptor clustering is thought to represent a critical parameter for neuronal transmission. Little is known about the mechanisms that anchor and concentrate inhibitory neurotransmitter receptors in neurons. GABA(A) receptor (GABA(A)R) alpha 5 subunits mainly locate at extrasynaptic sites and are thought to mediate tonic inhibition. Notably, similar as synaptic GABA(A)Rs, these receptor subtypes also appear in cluster formations at neuronal surface membranes and are of particular interest in cognitive processing. GABAAR alpha 5 mutation or depletion facilitates trace fear conditioning or improves spatial learning in mice, respectively. Here, we identified the actin-binding protein radixin, a member of the ERM family, as the first directly interacting molecule that anchors GABA(A)Rs at cytoskeletal elements. Intramolecular activation of radixin is a functional prerequisite for GABA(A)R alpha 5 subunit binding and both depletion of radixin expression as well as replacement of the radixin F-actin binding motif interferes with GABA(A)R alpha 5 cluster formation. Our data suggest radixin to represent a critical factor in receptor localization and/or downstream signaling.
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