Date of Degree

2009

Document Type

PhD diss.

Degree Name

PhD (Doctor of Philosophy)

Department

Neuroscience

First Advisor

Michael J. Welsh

Abstract

My thesis research comprises two projects looking into physiological functions of Drosophila ion channels: first, contribution of several T ransient R eceptor P otential (TRP) channels to gravity sensing; second, regulation of metabolic homeostasis by a D egenerin/ E pithelial Na + C hannel (DEG/ENaC).

Many animal species sense gravity for spatial orientation. In humans recurrent vertigo and dizziness are often attributable to impairment of gravity sensing in the vestibular organs. However, the molecular bases for gravity sensing and its disruption in vestibular disease remain uncertain. Here I studied gravity sensing in the model organism Drosophila melanogaster, with a combination of genetic, behavioral and electrophysiological methods. My results show that gravity sensing requires Johnston’s organ, a mechanosensory structure located in the antenna that also mediates hearing. Johnston’s organ neurons fire action potentials in a phasic manner in response to body rotations in the gravitational field. Furthermore, gravity sensing and hearing require different TRP channels with distinct anatomical localizations, implying separate neural mechanisms underlying gravity sensing and hearing. These findings set the stage for understanding how TRP channels contribute to the sensory transduction of gravity.

Drosophila melanogaster has over 20 genes belonging to the DEG/ENaC family, which are collectively referred to as pickpockets (ppks) . Genetic analyses have implicated ppk genes in salt taste, tracheal liquid clearance, pheromone detection, and developmental timing. These results, together with the conserved presence of DEG/ENaC genes through evolution, suggest that further studies on fly ppk genes may help gain insights to a number of physiological processes. Here I report that the ppk11 gene regulates metabolic homeostasis. A ppk11 enhancer/promoter fragment labels the fat body, the lipid storage organ of Drosophila. ppk11 mutants are lean — they store less triacylglyceride (TAG), possess smaller lipid droplets and are sensitive to starvation compared to wild–type flies. ppk11 mutants also show signs of enhanced insulin sensitivity — they store more glycogen and maintain a lower level of circulating carbohydrate (trehalose). Moreover, the mutants have extended life span, suggesting ppk11–dependent activities of the fat body have systematic and long–term effects on the fly body. Understanding the cellular function of ppk11 may offer new insights into mechanisms that regulate metabolic homeostasis.

Pages

xiii, 132

Bibliography

115-132

Copyright

Copyright 2009 Yishan Sun