agoraphobic modulates Notch receptor cleavage and signalling in Drosophila. H. Lopez-Schier , D. St Johnston. Wellcome/CRC, Univ Cambridge, Cambridge, England.

   Notch (N) is the key integrator of an evolutionarily conserved mechanism of intercellular communications. N encodes a large modular single-pass transmembrane receptor. Delta (Dl) and Serrate (Ser) are known N ligands. They are also single-pass transmembrane proteins with large extracellular domains. Upon ligand binding, a complex proteolitic processing of the N receptor allows its intracellular domain to translocate to the nucleus. The intracellular proteolisis event is dependent on presenilin (psn) function. We have identified a mutation called agoraphobic (agro) which specifically blocks N signalling by affecting the processing of the receptor. We have evidence which suggest that agro and psn activities are qualitatively different. We are currently analysing these differences and will present a detailed phenotypic analysis of mutant flies in order to clarify the function of agro in N signalling, and to explore its relationship to the psn-dependent processing of N.