title: C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1-PKCα complex and cerebellar plasticity.
abstract: BACKGROUND
  PICK1 (protein interacting with C-kinase 1) is a PKC (protein kinase C)-binding protein, which is essential for synaptic plasticity. The trafficking of PKCα-PICK1 complex to plasma membrane is critical for the internalization of GluR2 and induction of long-term depression. ICA69 (islet cell autoantigen 69 kDa) is identified as a major binding partner of PICK1. While heteromeric BAR domain complex is suggested to underlie the interaction between PICK1 and ICA69, the role of C-terminal domain of ICA69 (ICAC) in PICK1-ICA69 complex is unknown.
  
  
  RESULTS
  We found that ICAC interacted with PICK1 and regulated the trafficking of PICK1-PKCα complex. ICAC and ΔICAC (containing BAR domain) might function distinctly in the association of ICA69 with PICK1. While ΔICAC domain inclined to form clusters, the distribution of ICAC was diffuse. The trafficking of PICK1 to plasma membrane mediated by activated PKCα was inhibited by ICA69. This action might ascribe to ICAC, because overexpression of ICAC, but not ΔICAC, interrupted PKCα-mediated PICK1 trafficking. Notably, infusion of maltose binding protein (MBP) fusion protein, MBP-ICA69 or MBP-ICAC, in cerebellar Purkinje cells significantly inhibited the induction of long-term depression at parallel fiber- and climbing fiber-Purkinje cell synapses.
  
  
  CONCLUSIONS
  Our experiments showed that ICAC is an important domain for the ICA69-PICK1 interaction and plays essential roles in PICK1-mediated neuronal plasticity.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Li-Da
authors.initials: LD
authors.lastname: Su
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Center of Scientific Technology, Cranial Cerebral Disease Laboratory, Ningxia Medical University, Yinchuan, P. R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D021381:Protein Transport; D016415:Sequence Alignment
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C490185:Ica1 protein, rat; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D051571:Protein Kinase C-alpha