Max Perutz Labs, Center for Medical Biochemistry, Medical University of Vienna, Vienna Biocenter Campus (VBC), Vienna, Austria.
Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan, Israel.
Elife. 2021 Feb 19;10:e63476. doi: 10.7554/eLife.63476.
Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2α. Here, we show that loss of LAP2α actually causes formation of larger, biochemically stable lamin A/C structures in the nuclear interior that are inaccessible to lamin A/C antibodies. While nucleoplasmic lamin A forms from newly expressed pre-lamin A during processing and from soluble mitotic lamins in a LAP2α-independent manner, binding of LAP2α to lamin A/C during interphase inhibits formation of higher order structures, keeping nucleoplasmic lamin A/C in a mobile state independent of lamin A/C S22 phosphorylation. We propose that LAP2α is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.
在后生动物中，核纤层蛋白在核周形成稳定的纤维。与 B 型核纤层蛋白不同，核纤层蛋白 A 和 C 也定位于核内部，与核纤层相关多肽 2α（LAP2α）相互作用。我们之前使用抗体标记观察到，缺乏 LAP2α 的小鼠细胞中核质 A 型核纤层蛋白耗竭。在这里，我们表明 LAP2α 的缺失实际上会导致核内部更大、生化稳定的核纤层蛋白 A/C 结构的形成，这些结构对于核纤层蛋白 A/C 抗体是不可接近的。虽然核质核纤层 A 是在加工过程中从新表达的前核纤层 A 形成的，并且在 LAP2α 不依赖的方式下从有丝分裂核纤层中形成，但 LAP2α 与核纤层 A/C 的结合在有丝分裂间期抑制了更高阶结构的形成，使核质核纤层 A/C 处于与核纤层 A/C S22 磷酸化无关的可移动状态。我们提出 LAP2α 对于维持核内部的可移动核纤层 A/C 池是必需的，这对于适当的核功能是必需的。
