Soininen, Hilkka

Publication Detail

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Physiological role for casein kinase 1 in glutamatergic synaptic transmission.

Karima Chergui; Per Svenningsson; Paul Greengard (Profiled Author: Greengard, Paul)

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2005;25(28):6601-9.

Casein kinase 1 (CK1) is a highly conserved serine/threonine kinase, present in virtually all cell types, in which it phosphorylates a wide variety of substrates. So far, no role has been found for this ubiquitous protein kinase in the physiology of nerve cells. In the present study, we show that CK1 regulates fast synaptic transmission mediated by glutamate, the major excitatory neurotransmitter in the brain. Through the use of CK1 inhibitors, we present evidence that activation of CK1 decreases NMDA receptor activity in the striatum via a mechanism that involves activation by this kinase of protein phosphatase 1 and/or 2A and resultant increased dephosphorylation of NMDA receptors. Indeed, inhibition of CK1 increases NMDA-mediated EPSCs in medium spiny striatal neurons. This effect is associated with an increased phosphorylation of the NR1 and NR2B subunits of the NMDA receptor and is occluded by the phosphatase inhibitor okadaic acid. The mGluR1, but not mGluR5, subclass of metabotropic glutamate receptors uses CK1 to inhibit NMDA-mediated synaptic currents. These results provide the first evidence for a role of CK1 in the regulation of synaptic transmission in the brain.

2 Originating Grant

• 1.

  GREENGARD, PAUL

  DRUGS OF ABUSE - ROLE OF PROTEIN PHOSPHORYLATION

  1 March 1997 - 29 February 2016

  NATIONAL INSTITUTE ON DRUG ABUSE

  Total Funding: $ 24,977,507

• 2.

  Greengard, Paul

  REGION SPECIFIC PHOSPHOPROTEINS IN THE BASAL GANGLIA

  1 July 1985 - 30 June 2005

  NATIONAL INSTITUTE OF MENTAL HEALTH

  Total Funding: $ 27,221,874

Scientific Context

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