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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Boron Compounds / pharmacology
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Calcium / metabolism
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Calcium Signaling / genetics
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Calcium Signaling / physiology*
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism*
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Cell Cycle Proteins
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Cells, Cultured
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Cerebral Cortex / cytology
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Chelating Agents / pharmacology
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Dose-Response Relationship, Drug
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agents / pharmacology
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Immunoprecipitation / methods
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology*
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Neuronal Calcium-Sensor Proteins / antagonists & inhibitors
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Neuronal Calcium-Sensor Proteins / metabolism*
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Neurons / drug effects
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Neurons / physiology*
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Neuropeptides / antagonists & inhibitors
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Neuropeptides / metabolism*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism*
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Organ Culture Techniques
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Patch-Clamp Techniques
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Peptides / pharmacology
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RNA Interference / physiology
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RNA, Small Interfering / pharmacology
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Rats
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Receptors, Metabotropic Glutamate / genetics
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Receptors, Metabotropic Glutamate / physiology*
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Transfection / methods
Substances
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Boron Compounds
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Carrier Proteins
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Cell Cycle Proteins
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Chelating Agents
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Enzyme Inhibitors
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Excitatory Amino Acid Agents
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Neuronal Calcium-Sensor Proteins
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Neuropeptides
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Nuclear Proteins
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Peptides
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Prkcabp protein, mouse
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RNA, Small Interfering
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Receptors, Metabotropic Glutamate
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frequenin calcium sensor proteins
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MLCK peptide
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Egtazic Acid
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2-aminoethoxydiphenyl borate
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Calcium