Peter M, Nigg E A
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
J Cell Sci. 1991 Nov;100 ( Pt 3):589-98. doi: 10.1242/jcs.100.3.589.
The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. It is believed to be important for nuclear envelope integrity and the organization of interphase chromatin. On the basis of biochemical properties and sequence criteria, vertebrate lamin proteins are classified as either A- or B-type. While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines. Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development. These findings have led to the hypothesis that A-type lamins might play a role in establishing or stabilizing cell-type specific differences in nuclear organization, which in turn might relate to the developmental potential of a cell. To test this hypothesis, we have stably expressed chicken lamin A in undifferentiated murine embryonal carcinoma (P19) cells, and examined the consequences of ectopic lamin A expression for the differentiation state and potential of these cells. Our results demonstrate that the P19 cells, although normally devoid of lamin A, properly incorporate and process chicken lamin A. Moreover, the stably transfected cell lines maintain the properties of undifferentiated cells, demonstrating that expression of lamin A does not directly induce differentiation. Conversely, when exposed to retinoic acid, an inducer of differentiation, lamin A-expressing P19 cells are able to differentiate normally. Taken together, our results suggest that unscheduled expression of A-type lamins is not sufficient to deregulate cell differentiation programs. The implications of these findings for the possible role for lamin A expression during development are discussed.
核纤层是位于内核膜下方的中间丝类型网络。它被认为对核膜完整性和间期染色质的组织很重要。根据生化特性和序列标准，脊椎动物的核纤层蛋白可分为A型或B型。虽然B型核纤层蛋白在几乎所有细胞类型中都有表达，但在早期脊椎动物胚胎或未分化的胚胎癌细胞系中不存在A型核纤层蛋白。有趣的是，A型核纤层蛋白的表达与细胞分化和胚胎发育同时发生。这些发现导致了一个假说，即A型核纤层蛋白可能在建立或稳定核组织中细胞类型特异性差异方面发挥作用，而这反过来可能与细胞的发育潜能有关。为了验证这一假说，我们在未分化的小鼠胚胎癌（P19）细胞中稳定表达了鸡核纤层蛋白A，并研究了异位表达核纤层蛋白A对这些细胞的分化状态和潜能的影响。我们的结果表明，P19细胞虽然通常不含核纤层蛋白A，但能正确地整合和加工鸡核纤层蛋白A。此外，稳定转染的细胞系保持未分化细胞的特性，表明核纤层蛋白A的表达不会直接诱导分化。相反，当暴露于分化诱导剂视黄酸时，表达核纤层蛋白A的P19细胞能够正常分化。综上所述，我们的结果表明，A型核纤层蛋白的异常表达不足以破坏细胞分化程序。本文讨论了这些发现对核纤层蛋白A在发育过程中可能作用的影响。
