Mutagenesis and functional analysis of dveli, the Drosophila ortholog of C. elegans lin-7

Abstract

Proper assembly and localization of receptors and the associated signal transduction protein complex is important for normal cell function. Scaffolding proteins have been implicated in organizing the assembly of protein complex and localization of receptors. PDZ domain containing proteins are one major type of scaffolding protein. One well characterized system is the C. elegans LIN-2/LIN-7/LIN-10 PDZ protein complex. In C. elegans, this protein complex acts as a scaffold for the proper localization of LET-23, the ortholog of EGFR, to the epithelial basolateral membrane. The Drosophila orthologs, cmg, dveli and dmint/dX11L, have been identified. The sequence homologies and expression patterns suggest that these genes may have similar functions as their mammalian orthologs. The possible functions include cell-cell junction formation, receptor localization, ion channel localization and neurotransmitter vesicle trafficking. The main objectives of this thesis work are the mutagenesis and functional analysis of dveli. Potential mutants were generated by P element insertional mutagenesis, however, further analysis is required to identify the affected genes. A systemic RNAi experiment was performed. The delivery mechanism used was the RNAi soaking technique adapted from Dr. Davis’s laboratory protocol. Primary results from RNAi experiments show that loss of dveli function results in a reduction in larval locomotion speed. This slower locomotion phenotype along with the post-synaptic expression of dVELI at larval neuromuscular junction suggest a synaptic role of dVELI, perhaps aiding in synapse formation or proper localization of neurotransmitter receptors.