Ykt6, a conserved v-SNARE, is required in neuronal function and maintenance. Kai Li Tan¹, Shinya Yamamoto², Manish Jaiswal², Hector Sandoval², Gabriela David¹, Bo Xiong¹, Wu-Lin Charng¹, Ke Zhang⁴, Vafa Bayat³, Hugo J Bellen^1,2,4,5,6. 1) Program in Developmental Biology; 2) Department of Molecular and Human Genetics; 3) MSTP; 4) SCBMB Program; 5) HHMI; 6) Department of Neuroscience; Neurological Research Institute at Baylor of College of Medicine, Houston, TX.

   Membrane fusion is required for vesicular trafficking between various organelles and compartments. Many cell functions rely on membrane fusion, including intracellular transport, hormone or enzyme secretion and maturation of organelles. In particular, neurons utilize membrane fusion for activities that are important for neuronal function and maintenance such as neurotransmission, protein recycling and degradation. Some of the key players of membrane fusion are the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). In a forward genetic screen on the Drosophila X-chromosome to identify mutations that cause neurodegenerative phenotypes we identified 2 mutations in Ykt6, a gene that encodes the Drosophila homolog of mammalian Ykt6. Ykt6 is a highly conserved gene which encodes a v-SNARE. It is widely accepted that Ykt6 is involved in ER-Golgi anterograde transport based on yeast and mammalian studies. However, no mutants have been reported for Ykt6 in higher eukaryotes. Using the Ykt6 mutants, we examined the role of Ykt6 in photoreceptor function and maintenance. ERGs (electroretinogram recordings) of Ykt6 mutant clones show defects in neurotransmission, and a progressive decline of the amplitude of the ERGs as the flies age, a hallmark of neurodegeneration. The functional neurodegenerative phenotype was confirmed with TEM. We found that several photoreceptor-specific transmembrane proteins like Rhodopsin1 and Chaoptin are localized to the cell body rather than in the cell membrane. Biochemical studies suggest that these proteins are trapped in the ER. We are postulating that the accumulation of proteins in the ER in mutant photoreceptors leads to ER stress and neurodegeneration. This study will therefore be able to assess the role of Ykt6 in a multicellular organism in neuronal maintenance.