Molecular design principles for bipolar spindle organization by two opposing motors

• 成果类型: Article
• 署名作者: Chew, Wei-Xiang; Nedelec, Francois; Surrey, Thomas
• 署名单位: Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); University of Cambridge; Pompeu Fabra University; ICREA
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9454
• DOI: 10.1073/pnas.2422190122
• 发表日期: 2025-03-25
• 关键词: poleward microtubule flux; self-organization; cytoplasmic dynein; numa; DYNAMICS; motion; length

摘要

During cell division in animal cells, a bipolar spindle assembles to segregate the chromosomes. Various motor proteins with different properties are essential for spindle self- organization. The minimal set of components required to organize dynamic microtubules into a bipolar network remains however unknown. Here, we use computer simulations to explore whether two types of microtubule- crosslinking motors with opposite directionality can organize dynamic microtubules into bipolar spindles in three- dimensional space around a local microtubule nucleation source. We find that two motors are indeed sufficient, provided their properties resemble the main human spindle motors kinesin- 5 and dynein, revealing the core mechanism of spindle self- organization. It is based on the synergistic interplay of a slow plus- directed symmetric motor and a fast minus- directed asymmetric motor. A hypothetical symmetric minus- directed motor can also support spindle formation together with kinesin- 5, but only in a limited and unphysiological parameter range. In agreement with its accessory role in human cells, a minus motor with human kinesin- 14 properties does not assemble stable bipolar spindles together with kinesin- 5. These results reveal fundamental principles for the self- organization of dynamic bipolar microtubule architectures and highlight how distinct molecular designs of mitotic motors are optimized for their task.