Journal Article DKFZ-2017-03360

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

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2015
Oxford Univ. Press Oxford

Human molecular genetics 24(17), 4792 - 4808 () [10.1093/hmg/ddv204]
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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.

Keyword(s): Fatty Acids ; RNA, Messenger ; Sphingolipids ; LASS3 protein, mouse ; Sphingosine N-Acyltransferase

Classification:

Contributing Institute(s):
  1. AG Lipid-Pathobiochemie (G131)
  2. Zelluläre und Molekulare Pathologie (G130)
  3. Helmholtz-Professur Zellbiologie (A991)
Research Program(s):
  1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2015
Database coverage:
Medline ; Allianz-Lizenz / DFG ; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2017-09-26, last modified 2024-02-28



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