Daryabeigi Anahita, Woglar Alexander, Baudrimont Antoine, Silva Nicola, Paouneskou Dimitra, Vesely Cornelia, Rauter Manuel, Penkner Alexandra, Jantsch Michael, Jantsch Verena
Department of Chromosome Biology, Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030, Austria.
Center for Anatomy and Cell Biology, Department of Cell and Developmental Biology, Medical University of Vienna, 1090, Austria.
Genetics. 2016 Jun;203(2):733-48. doi: 10.1534/genetics.116.188094. Epub 2016 Apr 20.
SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1, and Syne homology) proteins are constituents of the inner and outer nuclear membranes. They interact in the perinuclear space via C-terminal SUN-KASH domains to form the linker of nucleoskeleton and cytoskeleton (LINC) complex thereby bridging the nuclear envelope. LINC complexes mediate numerous biological processes by connecting chromatin with the cytoplasmic force-generating machinery. Here we show that the coiled-coil domains of SUN-1 are required for oligomerization and retention of the protein in the nuclear envelope, especially at later stages of female gametogenesis. Consistently, deletion of the coiled-coil domain makes SUN-1 sensitive to unilateral force exposure across the nuclear membrane. Premature loss of SUN-1 from the nuclear envelope leads to embryonic death due to loss of centrosome-nuclear envelope attachment. However, in contrast to previous notions we can show that the coiled-coil domain is dispensable for functional LINC complex formation, exemplified by successful chromosome sorting and synapsis in meiotic prophase I in its absence.
SUN（Sad1和UNC-84）蛋白以及KASH（Klarsicht、ANC-1和Syne同源结构域）蛋白是内核膜和外核膜的组成成分。它们通过C端的SUN-KASH结构域在核周间隙相互作用，形成核骨架与细胞骨架连接物（LINC）复合体，从而跨越核被膜。LINC复合体通过将染色质与细胞质中的力产生机制相连，介导众多生物学过程。在此我们表明，SUN-1的卷曲螺旋结构域对于该蛋白在核被膜中的寡聚化及保留是必需的，尤其是在雌性配子发生的后期。一致的是，卷曲螺旋结构域的缺失使SUN-1对跨核膜的单侧力暴露敏感。SUN-1过早地从核被膜丢失会导致胚胎死亡，原因是中心体与核被膜的附着丧失。然而，与之前的观点相反，我们能够证明卷曲螺旋结构域对于功能性LINC复合体的形成并非必需，在其缺失的情况下减数分裂前期I中的染色体分类和联会成功就是例证。
