Activated radixin is essential for GABAA receptor alpha5 subunit anchoring at the actin cytoskeleton.
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. GABAA receptor (GABAAR) alpha5 subunits mainly locate at extrasynaptic sites and are thought to mediate tonic inhibition. Notably, similar as synaptic GABAARs, these receptor subtypes also appear in cluster formations at neuronal surface membranes and are of particular interest in cognitive processing. GABAAR alpha5 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 GABAARs at cytoskeletal elements. Intramolecular activation of radixin is a functional prerequisite for GABAAR alpha5 subunit binding and both depletion of radixin expression as well as replacement of the radixin F-actin binding motif interferes with GABAAR alpha5 cluster formation. Our data suggest radixin to represent a critical factor in receptor localization and/or downstream signaling.
Loebrich
Sven
S
Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Universität Hamburg, Hamburg, Germany.
Bähring
Robert
R
Katsuno
Tatsuya
T
Tsukita
Sachiko
S
Kneussel
Matthias
M
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D004594:Electrophysiology; D058787:GABA-A Receptor Antagonists; D015723:Gene Library; D006624:Hippocampus / Q000378:metabolism; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058787:GABA-A Receptor Antagonists; D008565:Membrane Proteins; D021122:Protein Subunits; D011963:Receptors, GABA-A; C073441:gephyrin; C071776:radixin