Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.
Rabionet, Mariona 1,2; Bayerle, Aline 1,2; Jennemann, Richard 2; Heid, Hans 3; Fuchser, Jens 4; Marsching, Christian 1,2,5; Porubsky, Stefan 6; Bolenz, Christian 7; Guillou, Florian 8; Grone, Hermann-Josef 2; Gorgas, Karin 9; Sandhoff, Roger 1,2,5,10,*
[Article] Human Molecular Genetics. 24(17):4792-4808, September 01, 2015.

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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.

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