Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1

J Jo, S Heon, MJ Kim, GH Son, Y Park, JM Henley, JL Weiss, M Sheng, GL Collingridge, K Cho

Research output: Contribution to journalArticle (Academic Journal)peer-review

84 Citations (Scopus)

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-Daspartate receptors(NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex, we have directly compared the Ca2+ signaling mechanisms involved in NMDAR-LTD and mGluRLTD. While both forms of LTD involve Ca2+ release from intracellular stores, the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal Ca2+ 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 Ca2+-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.
Translated title of the contributionMetabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1
Original languageEnglish
Pages (from-to)1095 - 1111
Number of pages17
JournalNeuron
Volume60
Issue number6
DOIs
Publication statusPublished - 26 Dec 2008

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