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 journalArticle

80 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

Fingerprint

Metabotropic Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Calmodulin
Synaptic Transmission
Synapses
Proteins
Phosphotransferases
Central Nervous System

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Metabotropic Glutamate Receptor-Mediated LTD Involves Two Interacting Ca2+ Sensors, NCS-1 and PICK1. / Jo, Jihoon; Heon, Seok; Kim, Myung Jong; Son, Gi Hoon; Park, Yunkyung; Henley, Jeremy M.; Weiss, Jamie L.; Sheng, Morgan; Collingridge, Graham L.; Cho, Kwangwook.

In: Neuron, Vol. 60, No. 6, 26.12.2008, p. 1095-1111.

Research output: Contribution to journalArticle

Jo, J, Heon, S, Kim, MJ, Son, GH, Park, Y, Henley, JM, Weiss, JL, Sheng, M, Collingridge, GL & Cho, K 2008, 'Metabotropic Glutamate Receptor-Mediated LTD Involves Two Interacting Ca2+ Sensors, NCS-1 and PICK1', Neuron, vol. 60, no. 6, pp. 1095-1111. https://doi.org/10.1016/j.neuron.2008.10.050
Jo, Jihoon ; Heon, Seok ; Kim, Myung Jong ; Son, Gi Hoon ; Park, Yunkyung ; Henley, Jeremy M. ; Weiss, Jamie L. ; Sheng, Morgan ; Collingridge, Graham L. ; Cho, Kwangwook. / Metabotropic Glutamate Receptor-Mediated LTD Involves Two Interacting Ca2+ Sensors, NCS-1 and PICK1. In: Neuron. 2008 ; Vol. 60, No. 6. pp. 1095-1111.
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