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Originally published In Press as doi:10.1074/jbc.M202947200 on April 5, 2002

J. Biol. Chem., Vol. 277, Issue 28, 25512-25518, July 12, 2002
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Identification and Characterization of a Sphingolipid Delta 4-Desaturase Family*

Philipp TernesDagger , Stephan Franke§, Ulrich Zähringer, Petra SperlingDagger , and Ernst HeinzDagger ||

From the Dagger  Institut für Allgemeine Botanik, Universität Hamburg, Ohnhorststr. 18, D-22609 Hamburg, Germany, the § Organische Mikroanalytik, Institut für Organische Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany, and the  Laborgruppe Immunchemie, Forschungszentrum Borstel, Parkallee 22, D-23845 Borstel, Germany

Sphingolipids desaturated at the Delta 4-position are important signaling molecules in many eukaryotic organisms, including mammals. In a bioinformatics approach, we now identified a new family of protein sequences from animals, plants, and fungi and characterized these sequences biochemically by expression in Saccharomyces cerevisiae. This resulted in the identification of the enzyme sphingolipid Delta 4-desaturase (dihydroceramide desaturase) from Homo sapiens, Mus musculus, Drosophila melanogaster, and Candida albicans, in addition to a bifunctional sphingolipid Delta 4-desaturase/C-4-hydroxylase from M. musculus. Among the sequences investigated are the Homo sapiens membrane lipid desaturase, the M. musculus degenerative spermatocyte, and the Drosophila melanogaster degenerative spermatocyte proteins. During spermatogenesis, but not oogenesis of des mutant flies, both cell cycle and spermatid differentiation are specifically blocked at the entry into the first meiotic division, leading to male sterility. This mutant phenotype can be restored to wild-type by complementation with a functional copy of the des gene (Endo, K., Akiyama, T., Kobayashi S., and Okada, M. (1996) Mol. Gen. Genet. 253, 157-165). These results suggest that Delta 4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during Drosophila spermatogenesis.

* This work was supported by Deutsche Forschungsgemeinschaft Grant He 695/15-1. Sequencing of C. albicans was accomplished with the support of the NIDR National Institutes of Health and the Burroughs Wellcome Fund.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF466375 (H. sapiens DES1), AF466376 (M. musculus DES1), AF466377 (M. musculus DES2), AF466378 (DES homologue L. esculentum), and AF466379 (D. melanogaster DES-1).

|| To whom correspondence should be addressed. Tel.: 49-40-42816-369; Fax: 49-40-42816-254; E-mail: eheinz@botanik.uni-hamburg.de.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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