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Molecular Pharmacology

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Altered G-Protein Coupling in an mGluR6 Point Mutant Associated with Congenital Stationary Night Blindness

Donald Beqollari, Matthew J. Betzenhauser and Paul J. Kammermeier
Molecular Pharmacology November 2009, 76 (5) 992-997; DOI: https://doi.org/10.1124/mol.109.058628
Donald Beqollari
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Matthew J. Betzenhauser
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Abstract

The highly specialized metabotropic glutamate receptor type 6 (mGluR6) is postsynaptically localized and expressed only in the dendrites of ON bipolar cells. Upon activation of mGluR6 by glutamate released from photoreceptors, a nonselective cation channel is inhibited, causing these cells to hyperpolarize. Mutations in this gene have been implicated in the development of congenital stationary night blindness type 1 (CSNB1). We investigated five known mGluR6 point mutants that lead to CSNB1 to determine the molecular mechanism of each phenotype. In agreement with other studies, four mutants demonstrated trafficking impairment. However, mGluR6 E775K (E781K in humans) suggested no trafficking or signaling deficiencies measured by our initial assays. Most importantly, our results indicate a switch in G-protein coupling, in which E775K loses Go coupling but retains coupling to Gi, which may explain the phenotype.

  • mGluR, metabotropic glutamate receptor
  • BBS, bungarotoxin binding site
  • CSNB, congenital stationary night blindness
  • SCG, superior cervical ganglion
  • HEK, human embryonic kidney
  • PTX, pertussis toxin
  • m3, muscarinic type 3 receptor
  • AM, acetoxymethyl ester
  • GFP, green fluorescent protein
  • i3, third intracellular loop
  • GLU, glutamate.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.109.058628

  • ABBREVIATIONS:

  • ↵1 Current affiliation: Department of Physiology and Cellular Biophysics, Columbia University, New York, New York.

    • Received June 16, 2009.
    • Accepted August 6, 2009.
  • © 2009 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 76 (5)
Molecular Pharmacology
Vol. 76, Issue 5
November 2009
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Altered G-Protein Coupling in an mGluR6 Point Mutant Associated with Congenital Stationary Night Blindness

Donald Beqollari, Matthew J. Betzenhauser and Paul J. Kammermeier
Molecular Pharmacology November 1, 2009, 76 (5) 992-997; DOI: https://doi.org/10.1124/mol.109.058628

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Altered G-Protein Coupling in an mGluR6 Point Mutant Associated with Congenital Stationary Night Blindness

Donald Beqollari, Matthew J. Betzenhauser and Paul J. Kammermeier
Molecular Pharmacology November 1, 2009, 76 (5) 992-997; DOI: https://doi.org/10.1124/mol.109.058628
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