Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling

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 r apamycin and as an important regulator of messenger RNA translation. In mam malian cells RAFT1 interacted with gephyrin, a widely expressed protein nec essary for the clustering of glycine receptors at the cell membrane of neur ons. RAFT1 mutants that could not associate with gephyrin failed to signal to downstream molecules, including the p70 ribosomal 56 kinase and the eIF- 4E binding protein, 4E-BP1. The interaction with gephyrin ascribes a functi on to the Large amino-terminal region of an ATM-related protein and reveals a role in signal transduction for the clustering protein gephyrin.