Department of Ophthalmology and Visual Sciences; Washington University School of Medicine; St Louis, MO USA; Division of Molecular Genetics; German Cancer Research Center (DKFZ); Heidelberg, Germany.
Nucleus. 2013 Sep-Oct;4(5):399-409. doi: 10.4161/nucl.26244. Epub 2013 Aug 23.
Sun proteins and Nesprins are two families of proteins whose direct interactions across the nuclear envelope provide for the core of Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) that physically connect the nucleus interior to cytoskeletal networks. Whereas LINC complexes play essential roles in nuclear migration anchorage and underlie normal CNS development, the developmental regulation of their composition remains largely unknown. In this study, we examined the spatiotemporal expression of lamins, Sun proteins and Nesprins during postnatal mouse retinal development. Whereas retinal precursor cells mostly express B-type lamins, Sun1, and high molecular weight isoforms of Nesprins, post-mitotic retinal cells are characterized by a drastic downregulation of the latter, the expression of A-type lamins, and the strong induction of a specific isoform of Nesprin1 late in retinal development. Importantly, our results emphasize different spatiotemporal expression for Nesprin1 and Nesprin2 and further suggest an important role for KASH-less isoforms of Nesprin1 in the CNS. In conclusion, the transition from retinal precursor cells undergoing interkinetic nuclear migration to post-mitotic retinal cells undergoing nuclear translocation and/or anchorage is accompanied by a profound remodeling of LINC complexes composition. This remodeling may reflect different requirements of nuclear dynamics at different stages of CNS development.
Sun 蛋白和 Nesprins 是两类蛋白,它们在核膜上的直接相互作用构成了核骨架到细胞骨架的连接(LINC 复合物)的核心,将细胞核内部与细胞骨架网络物理连接起来。尽管 LINC 复合物在核迁移锚定中发挥着重要作用,并为中枢神经系统的正常发育奠定了基础,但它们组成的发育调控在很大程度上仍是未知的。在这项研究中,我们研究了 lamin、Sun 蛋白和 Nesprins 在小鼠视网膜发育过程中的时空表达。虽然视网膜前体细胞主要表达 B 型 lamin、Sun1 和 Nesprins 的高分子量同工型,但有丝分裂后的视网膜细胞的特征是后者的表达急剧下调,A 型 lamin 的表达上调,以及在视网膜发育后期特异性 Nesprin1 同工型的强烈诱导。重要的是,我们的结果强调了 Nesprin1 和 Nesprin2 的不同时空表达,并进一步表明 KASH 缺失型 Nesprin1 同工型在中枢神经系统中具有重要作用。总之,从经历有丝分裂核迁移的视网膜前体细胞到经历核易位和/或锚定的有丝分裂后视网膜细胞的转变,伴随着 LINC 复合物组成的深刻重塑。这种重塑可能反映了中枢神经系统发育不同阶段核动力学的不同要求。