Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: A link to ceramide synthase-3

Mariona Rabionet, Aarnoud C. Van Der Spoel, Chia Chen Chuang, Benita Von Tümpling-Radosta, Manja Litjens, Diane Bouwmeester, Christina C. Hellbusch, Christian Körner, Herbert Wiegandt, Karin Gorgas, Frances M. Platt, Hermann Josef Gröne, Roger Sandhoff

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

96 Citas (Scopus)

Resumen

Previously, it was found that a novel class of neutral fucosylated glycosphingolipids (GSLs) is required for male fertility. These lipids contain very long-chain (C26-C32) polyunsaturated (4-6 double bonds) fatty acid residues (VLC-PUFAs). To assess the role of these complex GSLs in spermatogenesis, we have now investigated with which of the testicular cell types these lipids are associated. During postnatal development, complex glycosylated and simple VLC-PUFA sphingolipids were first detectable at day 15, when the most advanced germ cells are pachytene spermatocytes. Their synthesis is most likely driven by ceramide synthase-3. This enzyme is encoded by the Cers3/ Lass3 gene (longevity assurance genes), and out of six members of this gene family, only Cers3 mRNA expression was limited to germ cells, where it was up-regulated more than 700-fold during postnatal testicular maturation. Increasing levels of neutral complex VLC-PUFA GSLs also correlated with the progression of spermatogenesis in a series of male sterile mutants with arrests at different stages of spermatogenesis. Remarkably, fucosylation of the complex VLC-PUFA GSLs was not essential for spermatogenesis, as fucosylation-deficient mice produced nonfucosylated versions of the complex testicular VLC-PUFA GSLs, had complete spermatogenesis, and were fertile. Nevertheless, sterile Galgt1-/- mice, with a defective meiotic cytokinesis and a subsequent block in spermiogenesis, lacked complex but contained simple VLC-PUFA GSLs, as well as VLC-PUFA ceramides and sphingomyelins, indicating that the latter lipids are not sufficient for completion of spermatogenesis. Thus, our data imply that both glycans and the particular acyl chains of germinal sphingolipids are relevant for proper completion of meiosis.

Idioma originalEnglish
Páginas (desde-hasta)13357-13369
Número de páginas13
PublicaciónJournal of Biological Chemistry
Volumen283
N.º19
DOI
EstadoPublished - may. 9 2008
Publicado de forma externa

ASJC Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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