Drosophila Tempura, a novel Rab geranylgeranyl transferase subunit, modulates Notch signaling via Rab1 and Rab11. Wu-Lin Charng¹, Shinya Yamamoto^1,2, Manish Jaiswal^2,6, Vafa Bayat^1,3, Bo Xiong¹, Ke Zhang⁴, Hector Sandoval², Gabriela David¹, Hsiang-Chih Lu¹, Kuchuan Chen¹, Hugo Bellen^1,2,4,5,6. 1) Program in Developmental Biology; 2) Dept of Molecular and Human Genetics; 3) Medical Scientist Training Program; 4) Program in SCBMB; 5) Dept of Neuroscience; 6) Howard Hughes Medical Institute; The Neurological Research Institute; Baylor College of Medicine, Houston, TX.

   To identify novel players in Notch signaling we performed an F3 forward genetic screen and isolated an uncharacterized Drosophila gene, which we named tempura. temp mutants exhibit notum bristle loss and wing notching. The balding is caused by loss of Notch signaling during cell fate determination, as shown by multiple neurons per sensory cluster. In addition, the density of mutant sensory clusters is increased, indicating a Notch signaling defect during lateral inhibition. We observed an accumulation of Delta in sensory organs, which may be the cause of the cell fate defect. On the other hand, a positive Notch signaling modulator, Scabrous, cannot be properly secreted which leads to the lateral inhibition defect. temp homologs are found in all vertebrate species but have not been characterized in any model organisms. It encodes a protein with a domain showing homology to subunit of Rab geranylgeranyl transferase (RabGGT). This complex contains an and a subunit and adds geranylgeranyl groups to Rab proteins with the assistance of Rab escort protein (REP). Without this modification, Rab distribution is altered and vesicle trafficking is impaired. We propose that Temp functions as a novel subunit of RabGGT and modulates specific Rabs involved in trafficking of Notch signaling components. Indeed, Temp interacts with RabGGT subunit, REP, and Rabs. Overexpression of dominant negative Rab1 and Rab11 can phenocopy Sca accumulation and notum balding, respectively. We also observed a severe misdistribution of Rab1 and Rab11 in temp mutants. Hence, Temp modulates Rab1/Rab11 and regulates Notch signaling through Sca and Delta. We are currently testing whether this modulation also occurs in vertebrates.