Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Mol Biol Cell. 2013 Aug;24(15):2454-66. doi: 10.1091/mbc.E13-02-0100. Epub 2013 Jun 12.
Nesprin-3 is a nuclear envelope protein that connects the nucleus to intermediate filaments by interacting with plectin. To investigate the role of nesprin-3 in the perinuclear localization of plectin, we generated nesprin-3-knockout mice and examined the effects of nesprin-3 deficiency in different cell types and tissues. Nesprin-3 and plectin are coexpressed in a variety of tissues, including peripheral nerve and muscle. The expression level of nesprin-3 in skeletal muscle is very low and decreases during myoblast differentiation in vitro. Of interest, plectin was concentrated at the nuclear envelope in only a few cell types. This was most prominent in Sertoli cells of the testis, in which nesprin-3 is required for the localization of both plectin and vimentin at the nuclear perimeter. Testicular morphology and the position of the nucleus in Sertoli cells were normal, however, in the nesprin-3-knockout mice and the mice were fertile. Furthermore, nesprin-3 was not required for the polarization and migration of mouse embryonic fibroblasts. Thus, although nesprin-3 is critical for the localization of plectin to the nuclear perimeter of Sertoli cells, the resulting link between the nuclear envelope and the intermediate filament system seems to be dispensable for normal testicular morphology and spermatogenesis.
核膜蛋白 nesprin-3 通过与网蛋白相互作用将核连接到中间丝。为了研究 nesprin-3 在网蛋白的核周定位中的作用，我们生成了 nesprin-3 敲除小鼠，并在不同细胞类型和组织中研究了 nesprin-3 缺乏的影响。nesprin-3 和网蛋白在多种组织中共同表达，包括周围神经和肌肉。骨骼肌中 nesprin-3 的表达水平很低，并且在体外成肌细胞分化过程中降低。有趣的是，网蛋白仅在少数几种细胞类型中集中在核膜上。这在睾丸的支持细胞中最为明显，在这些细胞中，nesprin-3 对于网蛋白和波形蛋白在核周的定位都是必需的。然而，在 nesprin-3 敲除小鼠中，睾丸形态和支持细胞中的核位置正常，并且这些小鼠具有生育能力。此外，nesprin-3 对于小鼠胚胎成纤维细胞的极化和迁移不是必需的。因此，尽管 nesprin-3 对于网蛋白在支持细胞的核周定位至关重要，但核膜与中间丝系统之间的联系对于正常的睾丸形态和精子发生似乎是可有可无的。
