title: Cyclin Y inhibits plasticity-induced AMPA receptor exocytosis and LTP.
abstract: Cyclin Y (CCNY) is a member of the cyclin protein family, known to regulate cell division in proliferating cells. Interestingly, CCNY is expressed in neurons that do not undergo cell division. Here, we report that CCNY negatively regulates long-term potentiation (LTP) of synaptic strength through inhibition of AMPA receptor trafficking. CCNY is enriched in postsynaptic fractions from rat forebrain and is localized adjacent to postsynaptic sites in dendritic spines in rat hippocampal neurons. Using live-cell imaging of a pH-sensitive AMPA receptor, we found that during LTP-inducing stimulation, CCNY inhibits AMPA receptor exocytosis in dendritic spines. Furthermore, CCNY abolishes LTP in hippocampal slices. Taken together, our findings demonstrate that CCNY inhibits plasticity-induced AMPA receptor delivery to synapses and thereby blocks LTP, identifying a novel function for CCNY in post-mitotic cells.
authors.affiliation: 1] Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, South Korea [2] Department of Neuroscience, Korea University of Science and Technology, Daejeon 305-350, South Korea.
authors.forename: Eunsil
authors.initials: E
authors.lastname: Cho
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, BS1 3NY, UK.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
authors.forename: Young-Na
authors.initials: YN
authors.lastname: Hur
authors.affiliation: 1] Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, BS1 3NY, UK [2] Centre for Synaptic Plasticity, University of Bristol, Bristol, BS1 3NY, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Whitcomb
authors.affiliation: 1] Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, BS1 3NY, UK [2] Centre for Synaptic Plasticity, University of Bristol, Bristol, BS1 3NY, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Regan
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, South Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Ho Suh
authors.affiliation: 1] Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, BS1 3NY, UK [2] Centre for Synaptic Plasticity, University of Bristol, Bristol, BS1 3NY, UK.
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
authors.affiliation: 1] Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, South Korea [2] Department of Neuroscience, Korea University of Science and Technology, Daejeon 305-350, South Korea.
authors.forename: Mikyoung
authors.initials: M
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D059008:Time-Lapse Imaging
chemical_list: C000609447:Ccny protein, rat; D016213:Cyclins; D018091:Receptors, AMPA