First Author | Rabionet M | Year | 2015 |
Journal | Hum Mol Genet | Volume | 24 |
Issue | 17 | Pages | 4792-808 |
PubMed ID | 26045466 | Mgi Jnum | J:223367 |
Mgi Id | MGI:5648740 | Doi | 10.1093/hmg/ddv204 |
Citation | Rabionet M, et al. (2015) Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors. Hum Mol Genet 24(17):4792-808 |
abstractText | 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. |