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Glutamatergic regulation of serine racemase via reversal of PIP2 inhibition

Academic Article
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Overview

authors

  • Mustafaa, A. K.
  • van Rossum, D. B.
  • Patterson, R. L.
  • Maag, D.
  • Ehmsen, J. T.
  • Gazi, S. K.
  • Chakraborty, Anutosh
  • Barrow, R. K.
  • Amzel, L. M.
  • Snyder, S. H.

publication date

  • February 2009

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • D-serine is a physiologic coagonist with glutamate at NMDA-subtype glutamate receptors. As D-serine is localized in glia, synaptically released glutamate presumably stimulates the glia to form and release D-serine, enabling glutamate/D-serine cotransmission. We show that serine racemase (SR), which generates D-serine from L-serine, is physiologically inhibited by phosphatidylinositol (4,5)-bisphosphate (PIP2) presence in membranes where SR is localized. Activation of metabotropic glutamate receptors (mGluR5) on glia leads to phospholipase C-mediated degradation of PIP2, relieving SR inhibition. Thus mutants of SR that cannot bind PIP2 lose their membrane localizations and display a 4-fold enhancement of catalytic activity. Moreover, mGluR5 activation of SR activity is abolished by inhibiting phospholipase C.

subject areas

  • Adenosine Triphosphate
  • Binding, Competitive
  • Cell Line
  • Fluorescence Polarization
  • Glutamic Acid
  • Humans
  • Immunohistochemistry
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Binding
  • Racemases and Epimerases
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
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Research

keywords

  • D-serine
  • NMDA transmission
  • metabotropic glutamate receptor
  • phosphatidylinositol (4,5)-bisphosphate
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Identity

PubMed Central ID

  • PMC2635840

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0813105106

PubMed ID

  • 19193859
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Additional Document Info

start page

  • 2921

end page

  • 2926

volume

  • 106

issue

  • 8

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