Elkhatib Razan, Longepied Guy, Paci Marine, Achard Vincent, Grillo Jean-Marie, Levy Nicolas, Mitchell Michael J, Metzler-Guillemain Catherine
Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.
Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France APHM Hôpital La Conception, Gynépôle, Laboratoire de Biologie de la Reproduction-CECOS, 13385 Marseille Cedex 5, France.
Mol Hum Reprod. 2015 Mar;21(3):225-36. doi: 10.1093/molehr/gau111. Epub 2014 Dec 4.
The nuclear lamina (NL) is a filamentous protein meshwork, composed essentially of lamins, situated between the inner nuclear membrane and the chromatin. There is mounting evidence that the NL plays a role in spermatid differentiation during spermiogenesis. The mouse spermatid NL is composed of the ubiquitous lamin B1 and the spermatid-specific lamin B3, an N-terminally truncated isoform of lamin B2. However, nothing is known about the NL in human spermatids. We therefore investigated the expression pattern and localization of A-type lamins (A, C and C2) and B-type lamins (B1, B2 and B3) during human spermiogenesis. Here, we show that a lamin B3 transcript is present in human spermatids and that B-type lamins are the only lamins detectable in human spermatids. We determine that, as shown for their mouse counterparts, human lamin B3, but not lamin B2, induces strong nuclear deformation, when ectopically expressed in HeLa cells. Co-immunofluorescence revealed that, in human spermatids, B-type lamins are present at the nuclear periphery, except in the region covered by the acrosome, and that as the spermatid matures the B-type lamins recede towards the posterior pole. Only lamin B1 remains detectable on 33-47% of ejaculated spermatozoa. On spermatozoa selected for normal head density, however, this fell to <6%, suggesting that loss of the NL signal may be linked to complete sperm nucleus compaction. The similarities revealed between lamin expression during human and rodent spermiogenesis, strengthen evidence that the NL and lamin B3 have conserved functions during the intense remodelling of the mammalian spermatid nucleus.
核纤层(NL)是一种丝状蛋白质网络,主要由核纤层蛋白组成,位于内核膜和染色质之间。越来越多的证据表明,NL在精子发生过程中的精子细胞分化中发挥作用。小鼠精子细胞的NL由普遍存在的核纤层蛋白B1和精子细胞特异性核纤层蛋白B3组成,后者是核纤层蛋白B2的N端截短异构体。然而,关于人类精子细胞中的NL却一无所知。因此,我们研究了人类精子发生过程中A型核纤层蛋白(A、C和C2)和B型核纤层蛋白(B1、B2和B3)的表达模式和定位。在此,我们表明人类精子细胞中存在核纤层蛋白B3转录本,并且B型核纤层蛋白是人类精子细胞中唯一可检测到的核纤层蛋白。我们确定,正如在小鼠中所显示的那样,人类核纤层蛋白B3而非核纤层蛋白B2在HeLa细胞中异位表达时会诱导强烈的核变形。共免疫荧光显示,在人类精子细胞中,B型核纤层蛋白存在于核周边,但顶体覆盖的区域除外,并且随着精子细胞成熟,B型核纤层蛋白向后极退缩。在33 - 47%的射出精子中仅可检测到核纤层蛋白B1。然而,在选择头部密度正常的精子上,这一比例降至<6%,表明NL信号的丧失可能与精子细胞核的完全压实有关。人类和啮齿动物精子发生过程中核纤层蛋白表达之间的相似性,进一步证明了在哺乳动物精子细胞核的剧烈重塑过程中,NL和核纤层蛋白B3具有保守功能。