Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.
Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.
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DOI：
10.1093/hmg/ddv204
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发表时间：
2015-09
影响因子：
3.5
通讯作者：
M. Rabionet;Aline Bayerle;R. Jennemann;H. Heid;J. Fuchser;Christian Marsching;S. Porubský;C. Bolenz;F. Guillou;H. Gröne;K. Gorgas;R. Sandhoff
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作者：
M. Rabionet;Aline Bayerle;R. Jennemann;H. Heid;J. Fuchser;Christian Marsching;S. Porubský;C. Bolenz;F. Guillou;H. Gröne;K. Gorgas;R. Sandhoff
体细胞胞质分裂被证明涉及鞘脂（SL）插入到中间体之前，脱落。生精中间体转化为稳定的细胞间桥（ICBs），连接合胞体中的克隆子细胞。这个过程需要专门的SL结构。(1)使用高分辨率质谱成像，我们显示在原位的SL合成与睾丸特异性锚的双相模式。这种模式与神经酰胺合成酶3（CerS 3）的本地化，粗线期精母细胞，直到完成减数分裂和延长精子细胞。(2)在小鼠中阻断生殖细胞特异性神经酰胺（CerS 3-KO）和鞘糖脂（葡萄糖神经酰胺脱氢酶-KO）的途径突出了对精子细胞ICB稳定性的特殊SL的需求。与体细胞有丝分裂相反，这些SL需要具有独特物理化学性质的超长多不饱和锚，这只能由CerS 3提供。这些锚的丢失导致减数分裂过程中细胞凋亡增强，形成多核巨细胞和精子发生停滞。因此，睾丸特异性SL（我们也将其与人类睾丸中的CerS 3联系起来）是男性生育力的精髓。
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.