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Metabotropic Glutamate Receptor-mediated LTD Involves two Interacting Ca2+ Sensors, NCS-1 and PICK1

Published online by Cambridge University Press:  16 April 2020

J. Jo ,
S. Heon ,
M.J. Kim ,
G.H. Son ,
Y. Park ,
J.M. Henley ,
J.L. Weiss ,
M. Sheng ,
G.L. Collingridge  and
K. Cho
J. Jo
Affiliation:
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK
S. Heon
Affiliation:
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK
M.J. Kim
Affiliation:
The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, USA
G.H. Son
Affiliation:
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK
Y. Park
Affiliation:
Biomedical Science, University of Sheffield, Sheffield, UK
J.M. Henley
Affiliation:
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of BristolBristol, Bristol, UK
J.L. Weiss
Affiliation:
Biomedical Science, University of Sheffield, Sheffield, UK
M. Sheng
Affiliation:
The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, USA
G.L. Collingridge
Affiliation:
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of BristolBristol, Bristol, UK
K. Cho
Affiliation:
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK MRC Centre for Synaptic Plasticity, Department of Anatomy, University of BristolBristol, Bristol, UK

Abstract

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There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which 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+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst 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 is a component of a novel mechanism involved in mGluR-LTD.

Type
S17-01
Information
European Psychiatry , Volume 24 , Issue S1: 17th EPA Congress - Lisbon, Portugal, January 2009, Abstract book , January 2009 , 24-E84
Copyright
Copyright © European Psychiatric Association 2009
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