Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons.
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.
Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Yanmei
Y
Tao
Yong-Jun
YJ
Chen
Chengyong
C
Shen
Zhengyi
Z
Luo
C Ryan
CR
Bates
Daehoon
D
Lee
Sylvie
S
Marchetto
Tian-Ming
TM
Gao
Jean-Paul
JP
Borg
Wen-Cheng
WC
Xiong
Lin
L
Mei
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009043:Motor Activity / Q000235:genetics; D010320:Parvalbumins / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D002352:Carrier Proteins; C498804:Erbb2ip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010320:Parvalbumins; D018091:Receptors, AMPA; D005680:gamma-Aminobutyric Acid