TY  - JOUR
AU  - Rabionet, Mariona
AU  - Bayerle, Aline
AU  - Jennemann, Richard
AU  - Heid, Hans
AU  - Fuchser, Jens
AU  - Marsching, Christian
AU  - Porubsky, Stefan
AU  - Bolenz, Christian
AU  - Guillou, Florian
AU  - Gröne, Hermann-Josef
AU  - Gorgas, Karin
AU  - Sandhoff, Roger
TI  - Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors.
JO  - Human molecular genetics
VL  - 24
IS  - 17
SN  - 1460-2083
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2017-03360
SP  - 4792 - 4808
PY  - 2015
AB  - 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.
KW  - Fatty Acids (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Sphingolipids (NLM Chemicals)
KW  - LASS3 protein, mouse (NLM Chemicals)
KW  - Sphingosine N-Acyltransferase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26045466
DO  - DOI:10.1093/hmg/ddv204
UR  - https://inrepo02.dkfz.de/record/127335
ER  -