Developmental control of nuclear size and shape by kugelkern and kurzkern
Developmental control of nuclear size and shape by kugelkern and kurzkern
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DOI：
10.1016/j.cub.2006.01.051
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发表时间：
2006-03-21
期刊：
影响因子：
9.2
通讯作者：
Grosshans, J
中科院分区：
文献类型：
--
作者：
Brandt, A;Papagiannouli, F;Grosshans, J
背景：细胞核的形状取决于核纤层，核纤层与内核膜紧密相关，并与细胞骨架相互作用。然而，将细胞的分化状态与其细胞核形状变化相联系的机制尚未完全清楚。我们在果蝇早期胚胎中研究了这一问题，在细胞化过程中，细胞核形状从球形变为椭圆形，同时核长度增加了2.5倍。
结果：我们鉴定出两个对核伸长所必需的基因，kugelkern和kurzkern。在kugelkern和kurzkern缺失的胚胎中，在细胞化结束时，细胞核长度仅达到野生型细胞核的一半。核尺寸减小影响异染色质蛋白1标记的染色中心形成以及一组特定基因的表达，包括早期合子基因。kugelkern在蛋白质的N端一半包含一个假定的卷曲螺旋结构域、一个核定位信号（NLS）以及一个C端CxxM基序。羧基末端的CxxM基序是Kugelkern靶向内核膜所必需的，在那里它与核纤层蛋白共定位。根据法尼基化基序的不同，在果蝇胚胎或非洲爪蟾细胞中表达kugelkern会诱导核膜过度增殖。
结论：到目前为止，Kugelkern是除核纤层蛋白外第一个含有法尼基化位点的核蛋白。我们的研究结果表明，Kugelkern是核尺寸增加的一个速率决定因素。我们提出，法尼基化的Kugelkern与内核膜的结合诱导核表面积的扩展，从而允许核生长。
Background: The shape of a nucleus depends on the nuclear lamina, which is tightly associated with the inner nuclear membrane and on the interaction with the cytoskeleton. However, the mechanism connecting the differentiation state of a cell to the shape changes of its nucleus are not well understood. We investigated this question in early Drosophila embryos, where the nuclear shape changes from spherical to ellipsoidal together with a 2.5-fold increase in nuclear length during cellularization.Results: We identified two genes, kugelkern and kurzkern, required for nuclear elongation. In kugelkern- and kurzkern-depleted embryos, the nuclei reach only half the length of the wild-type nuclei at the end of cellularization. The reduced nuclear size affects chromocenter formation as marked by Heterochromatin protein 1 and expression of a specific set of genes, including early zygotic genes. kugelkern contains a putative coiled-coil domain in the N-terminal half of the protein, a nuclear localization signal (NLS), and a C-terminal CxxM-motif. The carboxyterminal CxxM motif is required for the targeting of Kugelkern to the inner nuclear membrane, where it colocalizes with lamins. Depending on the farnesylation motif, expression of kugelkern in Drosophila embryos or Xenopus cells induces overproliferation of nuclear membrane.Conclusions: Kugelkern is so far the first nuclear protein, except for lamins, that contains a farnesylation site. Our findings suggest that Kugelkern is a rate-determining factor for nuclear size increase. We propose that association of farnesylated Kugelkern with the inner nuclear membrane induces expansion of nuclear surface area, allowing nuclear growth.