title: Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.
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.
authors.affiliation: Lipid Pathobiochemistry Group, Department of Cellular and Molecular Pathology, Department of Cellular and Molecular Pathology .
authors.forename: Mariona
authors.initials: M
authors.lastname: Rabionet
authors.affiliation: Lipid Pathobiochemistry Group, Department of Cellular and Molecular Pathology, Department of Cellular and Molecular Pathology .
authors.forename: Aline
authors.initials: A
authors.lastname: Bayerle
authors.affiliation: Department of Cellular and Molecular Pathology .
authors.forename: Richard
authors.initials: R
authors.lastname: Jennemann
authors.affiliation: Helmholtz Group for Cell Biology, German Cancer Research Center (dkfz.), Heidelberg 69120, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Heid
authors.affiliation: Bruker Daltonik GmbH, Bremen 28359, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fuchser
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Marsching
authors.affiliation: Department of Pathology, University Medical Center Mannheim and .
authors.forename: Stefan
authors.initials: S
authors.lastname: Porubsky
authors.affiliation: Department of Urology, University Medical Center Mannheim, University of Heidelberg, Mannheim 68167, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.affiliation: Department of Cellular and Molecular Pathology .
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Department of Anatomy and Medical Cell Biology, University of Heidelberg, 69120, Germany and.
authors.forename: Karin
authors.initials: K
authors.lastname: Gorgas
authors.affiliation: 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.
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D048749:Cytokinesis; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007246:Infertility; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013091:Spermatogenesis; D013107:Sphingolipids / Q000096:biosynthesis / Q000378:metabolism*; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism / Q000473:pathology
chemical_list: D005227:Fatty Acids; D012333:RNA, Messenger; D013107:Sphingolipids; C513562:CerS3 protein, mouse; D051049:Sphingosine N-Acyltransferase