Human Molecular Genetics 2015-09-01

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

Mariona Rabionet, Aline Bayerle, Richard Jennemann, Hans Heid, Jens Fuchser, Christian Marsching, Stefan Porubsky, Christian Bolenz, Florian Guillou, Hermann-Josef Gröne, Karin Gorgas, Roger Sandhoff

文献索引：Hum. Mol. Genet. 24 , 4792-808, (2015)

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摘要

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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.