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Hum Mol Genet. 2015 Sep 1;24(17):4792-808. doi: 10.1093/hmg/ddv204. Epub 2015 Jun 4.

Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.

Author information

1
Lipid Pathobiochemistry Group, Department of Cellular and Molecular Pathology, Department of Cellular and Molecular Pathology .
2
Department of Cellular and Molecular Pathology .
3
Helmholtz Group for Cell Biology, German Cancer Research Center (dkfz.), Heidelberg 69120, Germany.
4
Bruker Daltonik GmbH, Bremen 28359, Germany.
5
Lipid Pathobiochemistry Group, Department of Cellular and Molecular Pathology, Department of Cellular and Molecular Pathology , Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim 68163, Germany.
6
Department of Pathology, University Medical Center Mannheim and .
7
Department of Urology, University Medical Center Mannheim, University of Heidelberg, Mannheim 68167, Germany.
8
INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.
9
Department of Anatomy and Medical Cell Biology, University of Heidelberg, 69120, Germany and.
10
Lipid Pathobiochemistry Group, Department of Cellular and Molecular Pathology, Department of Cellular and Molecular Pathology , Center for Applied Research "Applied Biomedical Mass Spectrometry" (ABIMAS), Mannheim 68163, Germany, Instrumental Analytics and Bioanalytics, Technical University of Applied Sciences Mannheim, Mannheim 69120, Germany r.sandhoff@dkfz.de r.sandhoff@hs-mannheim.de.

Abstract

Somatic cell cytokinesis was shown to involve the insertion of sphingolipids (SLs) to midbodies prior to abscission. Spermatogenic midbodies transform into stable intercellular bridges (ICBs) connecting clonal daughter cells in a syncytium. This process requires specialized SL structures. (1) Using high resolution-mass spectrometric imaging, we show in situ a biphasic pattern of SL synthesis with testis-specific anchors. This pattern correlates with and depends on ceramide synthase 3 (CerS3) localization in both, pachytene spermatocytes until completion of meiosis and elongating spermatids. (2) Blocking the pathways to germ cell-specific ceramides (CerS3-KO) and further to glycosphingolipids (glucosylceramide synthase-KO) in mice highlights the need for special SLs for spermatid ICB stability. In contrast to somatic mitosis these SLs require ultra-long polyunsaturated anchors with unique physico-chemical properties, which can only be provided by CerS3. Loss of these anchors causes enhanced apoptosis during meiosis, formation of multinuclear giant cells and spermatogenic arrest. Hence, testis-specific SLs, which we also link to CerS3 in human testis, are quintessential for male fertility.

PMID:
26045466
DOI:
10.1093/hmg/ddv204
[Indexed for MEDLINE]

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