| The Drosophila inebriated (ine) gene encodes a putative transporter (Ine) that shares high homology to members of the Na+/Cl− dependent neurotransmitter transporter family. Mutations in the ine gene were found to cause increased neuronal excitability. Research documented in this thesis demonstrated that ine also confers defective osmotic stress response, confirming the dual roles played by certain members of this family in regulating both neuronal excitability and osmotic stress response. In addition, from further investigation of the neuronal phenotypes of ine mutants it was discovered that Ine might act in short-term to affect neuronal excitability, that the transporter can exert its function from either neurons or glia, and that the two isoforms of the transporter, Ine-P1 and Ine-P2, which are identical in major portion of their sequence but differ in their N termini, are both capable of their function in the absence of the other, although the former functions more efficiently. Furthermore, ine overexpression causes phenotypes that closely resemble those of mutants with defective sodium channels. These phenotypes include delayed onset of long-term facilitation, suppression of the leg-shaking phenotypes of Shaker , temperature sensitive paralysis, enhancement of the paralytic (para) mutation, increased failure rate of transmitter release at the larval neuromuscular junction, reduced amplitude of larval nerve compound action potential and failure of compound action potential at restrictive temperature. Taken together, these observations raise the possibility that ine might be involved in a signaling pathway that regulates neuronal sodium channels. |
