PICK1 mediates synaptic recruitment of AMPA receptors at neurexin-induced postsynaptic sites.
In the CNS, synapse formation and maturation play crucial roles in the construction and consolidation of neuronal circuits. Neurexin and neuroligin localize on the opposite sides of synaptic membrane and interact with each other to promote the assembly and specialization of synapses. However, the excitatory synapses induced by the neurexin-neuroligin complex are initially immature synapses that lack AMPA receptors. Previously, PICK1 (protein interacting with C kinase 1) was shown to cluster and regulate the synaptic localization of AMPA receptors. Here, we report that during synaptogenesis induced by neurexin in cultured neurons from rat hippocampus, PICK1 recruited AMPA receptors to immature postsynaptic sites. This synaptic recruitment of AMPA receptors depended on the interaction between GluA2 and PICK1, and on the lipid-binding ability of PICK1, but not the interaction between PICK1 and neuroligin. Last, our results demonstrated that the recruitment of GluA2 to synapses could be prevented by ICA69 (islet cell autoantigen 69 kDa), a key binding partner of PICK1. Our study showed that PICK1, being negatively regulated by ICA69, could facilitate synapse maturation.
Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 100044, People's Republic of China, and Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, People's Republic of China.
Junyu
J
Xu
Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 100044, People's Republic of China, and.
Chuen
C
Kam
Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, People's Republic of China.
Jian-Hong
JH
Luo
Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 100044, People's Republic of China, and jxia@ust.hk.
Jun
J
Xia
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D018091:Receptors, AMPA / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011999:Recruitment, Neurophysiological / Q000235:genetics / Q000502:physiology*
D001324:Autoantigens; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; C490184:Ica1 protein, mouse; C547193:Nrxn1 protein, rat; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; C093438:neuroligin 1; C104722:glutamate receptor ionotropic, AMPA 2
AMPA receptor; PICK1; neurexin; neuroligin; silent synapse; synapse maturation