Genetics, Vol. 165, 1243-1253, November 2003, Copyright © 2003
A Temperature-Sensitive Allele of Drosophila sesB Reveals Acute Functions for the Mitochondrial Adenine Nucleotide Translocase in Synaptic Transmission and Dynamin Regulation
Richa Rikhya,
Mani Ramaswamib, and
K. S. Krishnana
a Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai 400005, India
b Department of Molecular and Cellular Biology and Division of Neurobiology, University of Arizona, Tucson, Arizona 85721
Corresponding author:
K. S. Krishnan, Tata Institute of Fundamental Research, Homi Bhabha Rd., Colaba, Mumbai 400005, India. E-mail:ksk@tifr.res.in
Communicating editor: T. KAUFMAN
Rapidly reversible, temperature-sensitive (ts) paralytic mutants of Drosophila have been useful in delineating immediate in vivo functions of molecules involved in synaptic transmission. Here we report isolation and characterization of orangi (org), an enhancer of shibire (shi), a ts paralytic mutant in Drosophila dynamin. org is an allele of the stress sensitive B (sesB) locus that encodes a mitochondrial adenine nucleotide translocase (ANT) and results in a unique ts paralytic behavior that is accompanied by a complete loss of synaptic transmission in the visual system. sesBorg reduces the restrictive temperature for all shits alleles tested except for shits1. This characteristic allele-specific interaction of sesBorg with shi is shared by abnormal wing discs (awd), a gene encoding nucleoside diphosphate kinase (NDK). sesBorg shows independent synergistic interactions, an observation that is consistent with a shared pathway by which org and awd influence shi function. Genetic and electrophysiological analyses presented here, together with the observation that the sesBorg mutation reduces biochemically assayed ANT activity, suggest a model in which a continuous mitochondrial ANT-dependent supply of ATP is required to sustain NDK-dependent activation of presynaptic dynamin during a normal range of synaptic activity.