Sec15 promotes Notch signaling during asymmetric division of Drosophila sensory organ precursors via an interaction with Rab11

Hillary K Andrews1, Shuya Wu2, Hamed Jafar-Nejad3, Flo Quiocho2, Hugo J Bellen1,3,4. 1) Program in Developmental Biology, Baylor College of Medicine, Houston, TX; 2) Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX; 3) Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; 4) HHMI, Baylor College of Medicine, Houston, TX.

Asymmetric division of sensory organ precursors (SOPs) in Drosophila generates the different cell types of the mature sensory organ. In a genetic screen designed to identify novel players in this process, we isolated a mutation in Drosophila sec15, which encodes a component of the exocyst, an evolutionarily conserved complex implicated in intracellular vesicle transport. Loss of sec15 function results in the generation of extra neurons at the expense of support cells, a phenotype compatible with loss of Notch signaling. Although sec15 mutant cells are able to establish apical-basal polarity, a vesicular compartment containing Notch, Sanpodo and endocytosed Delta accumulates in the basal areas of mutant SOPs. Sec15 shows a dynamic trafficking pattern and colocalizes with the recycling endosomal marker Rab11 in wild-type SOPs. Based on the aberrant distribution of Rab11 in sec15 clones, we propose that a defect in Delta recycling causes cell fate transformation in sec15- sensory lineages. Based on the crystal structure of Sec15 and Rab11, we have identified specific amino acids required for binding to Rab11 in vitro. To test our model for Sec15-Rab11 function in Notch signaling, we have created transgenic flies which contain point mutations in the Rab11 binding domain of Sec15. Our data indicate that Sec15 and Rab11 mediate a specific vesicle trafficking event which ensures proper neuronal fate specification in Drosophila.

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