Kinetochore proteins control microtubule dynamics in postmitotic neurons to regulate the formation of dendritic spines

• 成果类型: Article
• 署名作者: Zhao, Guoli; Sharma, Aditi; Tang, Jing; Aleman, Martina; Liang, Xing; Miner, Lauren; Qi, Jingqi; Xiang, Wangchu; Tian, Feng; Goldberg, Yves; He, Zhigang; Shen, Kang; Peris, Leticia; Schwarz, Thomas L.
• 署名单位: Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; CEA; Communaute Universite Grenoble Alpes; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Grenoble Alpes (UGA); Stanford University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Stanford University; Stanford Medicine; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2520684123
• 发表日期: 2026-05-05
• 页码: e2520684123
• 关键词: kinetochore; microtubule; Ndc80; iNeuron; dendritic spine; AXONAL GROWTH; MOTOR PROTEIN; KINESIN-12; binding; memory; actin

摘要

Kinetochore proteins, long studied for their role in cell division, are also required for the proper postmitotic development of hippocampal and cortical neurons. Proteins of the kinetochore complex were present in axons and dendrites of postmitotic iNeurons where they resided, at least in part, at microtubule plus ends. Conditional deletion of mouse Ndc80 or Dsn1 increased the number of dendritic spines. Loss of any of three kinetochore components (Ndc80, Dsn1, or Mis12) increased microtubule plus-end dynamics. Observations of individual microtubules in Caenorhabditis elegans indicated that Ndc80, the microtubule-binding component of the kinetochore complex, slowed the rate of microtubule growth. The increase in spine number in mammalian neurons correlated with increased microtubule invasion of spines. Both spine number and microtubule invasion phenotypes induced by Ndc80 deletion could be rescued by reexpression of Ndc80, but only if the microtubule-binding region of NDC80 was preserved. We propose that kinetochore proteins act in a complex resembling the mitotic kinetochore in order to stabilize microtubule plus ends and thereby restrain spine invasions and the development of dendritic spines.