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Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons
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Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons
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Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons
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Journal Article
Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons
2013
Overview
This study describes the synaptogenic function of an ErbB2-interacting protein called Erbin, particularly its function in the formation of excitatory synapses on interneurons and its regulation of AMPA-type glutamate receptors through its interaction with the auxiliary AMPA receptor protein TARP γ-2.
Inhibitory neurons control the firing of glutamatergic neurons and synchronize brain activity. However, little is known about mechanisms of excitatory synapse formation in inhibitory neurons. Here we demonstrate that Erbin is specifically expressed in cortical inhibitory neurons. It localizes at excitatory synapses and regulates AMPA receptor (AMPAR) surface expression. Erbin mutation reduced mEPSCs and AMPAR currents specifically in parvalbumin (PV)-positive interneurons but not in pyramidal neurons. We found that the AMPAR auxiliary protein TARP γ-2 was specifically expressed in cortical interneurons. Erbin interacts with TARP γ-2 and is crucial for its stability. Deletion of the γ-2–interacting domain in Erbin attenuated surface AMPAR and excitatory transmission in PV-positive interneurons. Furthermore, we observed behavioral deficits in Erbin-null mice and in mice expressing an Erbin truncation mutant that is unable to interact with TARP γ-2. These observations demonstrate a crucial function for Erbin in AMPAR surface expression in cortical PV-positive interneurons and may contribute to a better understanding of psychiatric disorders.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Behavior, Animal - physiology
/ Calcium Channels - metabolism
/ Carrier Proteins - metabolism
/ Cerebral Cortex - metabolism
/ Excitatory Postsynaptic Potentials - physiology
/ gamma-Aminobutyric Acid - metabolism
/ Humans
/ Mice
/ Miniature Postsynaptic Potentials - physiology
/ Neurons
/ Receptors, AMPA - metabolism
/ Synapses
