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Science 14 May 1999:
Vol. 284. no. 5417, pp. 1161 - 1164
DOI: 10.1126/science.284.5417.1161
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Reports

Interaction of RAFT1 with Gephyrin Required for Rapamycin-Sensitive Signaling

David M. Sabatini, 1* Roxanne K. Barrow, 1 Seth Blackshaw, 1 Patrick E. Burnett, 1 Michael M. Lai, 1 Michael E. Field, 1 Ben A. Bahr, 2 Joachim Kirsch, 3 Heinrich Betz, 3 Solomon H. Snyder 1dagger

RAFT1 (rapamycin and FKBP12 target 1; also called FRAP or mTOR) is a member of the ATM (ataxia telangiectasia mutated)-related family of proteins and functions as the in vivo mediator of the effects of the immunosuppressant rapamycin and as an important regulator of messenger RNA translation. In mammalian cells RAFT1 interacted with gephyrin, a widely expressed protein necessary for the clustering of glycine receptors at the cell membrane of neurons. RAFT1 mutants that could not associate with gephyrin failed to signal to downstream molecules, including the p70 ribosomal S6 kinase and the eIF-4E binding protein, 4E-BP1. The interaction with gephyrin ascribes a function to the large amino-terminal region of an ATM-related protein and reveals a role in signal transduction for the clustering protein gephyrin.

1 The Johns Hopkins University School of Medicine, Department of Neuroscience, 725 North Wolfe Street, Baltimore, MD 21205, USA.
2 Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
3 Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt/Main, Germany.
*   Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.

dagger    To whom correspondence should be addressed. E-mail: ssnyder{at}jhmi.edu

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