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  • 标题:Mechanistic insights into central spindle assembly mediated by the centralspindlin complex
  • 本地全文:下载
  • 作者:Han Pan ; Ruifang Guan ; Ruixue Zhao
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2021
  • 卷号:118
  • 期号:40
  • DOI:10.1073/pnas.2112039118
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Significance Centralspindlin bundles microtubules to assemble the central spindle, being essential for cytokinesis of the cell. It is a heterotetramer formed by ZEN-4 and CYK-4 in a 2:2 manner. We determined the crystal structures of centralspindlin, which revealed the detailed mechanism of complex formation. We found that centralspindlin clustered to undergo liquid–liquid phase separation (LLPS), which depended on the complementary charged residues located at ZEN-4 and CYK-4, respectively, explaining the synergy of the two subunits for the function. The LLPS of centralspindlin is critical for the microtubule bundling activity in vitro and the assembly of the central spindle in vivo. Together, our study provides angstrom-to-micron mechanistic insights into central spindle assembly mediated by the centralspindlin complex. The central spindle spatially and temporally regulates the formation of division plane during cytokinesis in animal cells. The heterotetrameric centralspindlin complex bundles microtubules to assemble the central spindle, the mechanism of which is poorly understood. Here, we determined the crystal structures of the molecular backbone of ZEN-4/CYK-4 centralspindlin from Caenorhabditis elegans, which revealed the detailed mechanism of complex formation. The molecular backbone of centralspindlin has the intrinsic propensity to undergo liquid–liquid phase separation. The condensation of centralspindlin requires two patches of basic residues at ZEN-4 and multiple acidic residues at the intrinsically disordered region of CYK-4, explaining the synergy of the two subunits for the function. These complementary charged residues were critical for the microtubule bundling activity of centralspindlin in vitro and for the assembly of the central spindle in vivo. Together, our findings provide insights into the mechanism of central spindle assembly mediated by centralspindlin through charge-driven macromolecular condensation.
  • 关键词:encentralspindlin;microtubule;cytokinesis;ZEN-4;CYK-4
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