Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Centre for Integrative Biological Signalling Studies-CIBSS, University of Freiburg, Freiburg, Germany.
EMBO Rep. 2024 Nov;25(11):4728-4748. doi: 10.1038/s44319-024-00274-8. Epub 2024 Sep 24.
The nucleoskeleton is essential for nuclear architecture as well as genome integrity and gene expression. In addition to lamins, titin or spectrins, dynamic actin filament polymerization has emerged as a potential intranuclear structural element but its functions are less well explored. Here we found that calcium elevations trigger rapid nuclear actin assembly requiring the nuclear membrane protein SUN2 independently of its function as a component of the LINC complex. Instead, SUN2 colocalized and associated with the formin and actin nucleator INF2 in the nuclear envelope in a calcium-regulated manner. Moreover, SUN2 is required for active RNA polymerase II (RNA Pol II) clustering in response to calcium elevations. Thus, our data uncover a SUN2-formin module linking the nuclear envelope to intranuclear actin assembly to promote signal-dependent spatial reorganization of active RNA Pol II.
核骨架对于核架构以及基因组完整性和基因表达至关重要。除了核纤层蛋白、肌联蛋白或 spectrins 外，动态肌动蛋白丝聚合已成为一种潜在的核内结构元件，但它的功能尚未得到充分探索。在这里，我们发现钙升高会触发快速的核肌动蛋白组装，这需要核膜蛋白 SUN2，而与 SUN2 作为 LINC 复合物的组成部分的功能无关。相反，SUN2 以钙调节的方式与核膜中的形成蛋白和肌动蛋白成核因子 INF2 共定位和相关。此外，SUN2 是钙升高时活性 RNA 聚合酶 II（RNA Pol II）聚集所必需的。因此，我们的数据揭示了一个 SUN2-形成蛋白模块，将核膜与核内肌动蛋白组装连接起来，以促进活性 RNA Pol II 信号依赖性的空间重排。
