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Publication - Professor Graham Collingridge

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

    Citation

    Jo, J, Heon, S, Kim, M, Son, G, Park, Y, Henley, J, Weiss, J, Sheng, M, Collingridge, G & Cho, K, 2008, ‘Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1’. Neuron, vol 60., pp. 1095 - 1111

    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.

    Full details in the University publications repository