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

90 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
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Royal Society (K.C.), the BBSRC (K.C. and J.L.W.), Brain Research Center of the 21st Century Frontier Research Program funded by the Korean Ministry of Science and Technology (K.C. and G.L.C.), and the MRC (G.L.C.). We thank Dr. Sang-Hyoung Lee for the GluR1 constructs, Dr. Jonathan Hanley for the PICK1 constructs, and Dr. Robert Levenson (Penn State) for the NCS-1fusion protein constructs. M.S. is an Investigator of the Howard Hughes Medical Institute. G.L.C. is a Wolfson-Royal Society fellow.

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • General Neuroscience

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