The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis.
Certain gene mutations in Drosophila melanogaster cause sluggish motor activity. We have localized the transcription unit of the sluggish-A gene to a 14.7-kb region at the base of the X chromosome and have cloned corresponding cDNAs. The predicted protein product has significant sequence similarity to Saccharomyces cerevisiae proline oxidase (EC 1.5.99.8), a mitochondrial enzyme which catalyzes the first step in the conversion of proline to glutamate. In the mutant fly, mitochondrial proline oxidase activity is reduced and has kinetic properties different from those of the wild type, providing further evidence that the gene encodes proline oxidase. Indeed, the free proline level in mutant flies is elevated. When the mutant is rescued by transformation, the proline oxidase and free proline levels, as well as the motor and phototactic behavior, are restored to normal. During embryonic development the sluggish-A transcript is predominantly expressed in the nervous system. Significantly, it has previously been reported that a mouse mutant, PRO/Re, which has reduced proline oxidase activity and elevated free proline levels, also exhibits sluggish behavior.
Hayward
D C
DC
Research School of Biological Sciences, Australian National University, Canberra, ACT.
Delaney
S J
SJ
Campbell
H D
HD
Ghysen
A
A
Benzer
S
S
Kasprzak
A B
AB
Cotsell
J N
JN
Young
I G
IG
Miklos
G L
GL
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D015342:DNA Probes; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D005971:Glutamates / Q000096:biosynthesis*; D018698:Glutamic Acid; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009043:Motor Activity; D009154:Mutation; D009420:Nervous System / Q000201:enzymology*; D009424:Nervous System Physiological Phenomena; D011394:Proline Oxidase / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D015342:DNA Probes; D005971:Glutamates; D018698:Glutamic Acid; D011394:Proline Oxidase