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The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis

Hayward, D. C. and Delaney, S. J. and Campbell, H. D. and Ghysen, A. and Benzer, S. and Kasprzak, A. B. and Cotsell, J. N. and Young, I. G. and Miklos, G. L. Gabor (1993) The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis. Proceedings of the National Academy of Sciences of the United States of America, 90 (7). pp. 2979-2983. ISSN 0027-8424. PMCID PMC46220. https://resolver.caltech.edu/CaltechAUTHORS:20141216-111748677

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Abstract

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.


Item Type:Article
Related URLs:
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http://dx.doi.org/10.1073/pnas.90.7.2979DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46220/PubMed CentralArticle
Additional Information:© 1993 National Academy of Sciences. Contributed by S. Benzer, December 23, 1992. We thank Doug Kankel for advice concerning the free amino acid determinations and the excitatory amino acid literature. We thank P. Milburn and B. Presnell of the Australian National University Biomolecular Resource Facility for amino acid analysis and James Whitehead and Jeff Wilson for illustration and photographic assistance. This work was in part supported by Grant BCS-8908154 (to S.B.) from the National Science Foundation. The sequence reported in this paper has been deposited in the GenBank data base (accession no. L07330).
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Funding AgencyGrant Number
NSFBCS-8908154
Issue or Number:7
PubMed Central ID:PMC46220
Record Number:CaltechAUTHORS:20141216-111748677
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141216-111748677
Official Citation:The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis D C Hayward, S J Delaney, H D Campbell, A Ghysen, S Benzer, A B Kasprzak, J N Cotsell, I G Young, and G L Miklos PNAS 1993 90 (7) 2979-2983
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52868
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:16 Dec 2014 19:59
Last Modified:03 Oct 2019 07:45

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