title: Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1.
abstract: There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system that require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex, we have directly compared the Ca(2+) signaling mechanisms involved in NMDAR-LTD and mGluR-LTD. While both forms of LTD involve Ca(2+) release from intracellular stores, the Ca(2+) sensors involved are different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal Ca(2+) sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC, as well as protein interacting with C kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1 via its BAR domain in a Ca(2+)-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 plays a distinct role in mGluR-LTD.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Jo
authors.forename: Seok
authors.initials: S
authors.lastname: Heon
authors.forename: Myung Jong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Gi Hoon
authors.initials: GH
authors.lastname: Son
authors.forename: Yunkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Henley
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Weiss
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D047468:Immunoprecipitation / Q000379:methods; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051580:Neuronal Calcium-Sensor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D001896:Boron Compounds; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D010455:Peptides; C091822:Prkcabp protein, mouse; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; C101464:frequenin calcium sensor proteins; C065738:MLCK peptide; D004533:Egtazic Acid; C109986:2-aminoethoxydiphenyl borate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium