Metabotropic Glutamate Receptor-Mediated LTD Involves Two Interacting Ca2+ Sensors, NCS-1 and PICK1

Jihoon Jo, Seok Heon, Myung Jong Kim, Gi Hoon Son, Yunkyung Park, Jeremy M. Henley, Jamie L. Weiss, Morgan Sheng, Graham L. Collingridge, Kwangwook Cho

Research output: Contribution to journalArticlepeer-review

81 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-D-aspartate 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 mGluR-LTD. 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.

Original languageEnglish
Pages (from-to)1095-1111
Number of pages17
JournalNeuron
Volume60
Issue number6
DOIs
Publication statusPublished - 2008 Dec 26

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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