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Science 13 November 1998:
Vol. 282. no. 5392, pp. 1321 - 1324
DOI: 10.1126/science.282.5392.1321
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Reports

Dual Requirement for Gephyrin in Glycine Receptor Clustering and Molybdoenzyme Activity

Guoping Feng, * Hartmut Tintrup, * Joachim Kirsch, Mia C. Nichol, Jochen Kuhse, Heinrich Betz, Joshua R. Sanes dagger

Glycine receptors are anchored at inhibitory chemical synapses by a cytoplasmic protein, gephyrin. Molecular cloning revealed the similarity of gephyrin to prokaryotic and invertebrate proteins essential for synthesizing a cofactor required for activity of molybdoenzymes. Gene targeting in mice showed that gephyrin is required both for synaptic clustering of glycine receptors in spinal cord and for molybdoenzyme activity in nonneural tissues. The mutant phenotype resembled that of humans with hereditary molybdenum cofactor deficiency and hyperekplexia (a failure of inhibitory neurotransmission), suggesting that gephyrin function may be impaired in both diseases.

G. Feng, M. C. Nichol, J. R. Sanes, Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. H. Tintrup, J. Kirsch, J. Kuhse, H. Betz, Department of Neurochemistry, Max-Planck Institute for Brain Research, Frankfurt 60528, Germany.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: sanesj{at}thalamus.wustl.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)