近日，德国马克斯·普朗克多学科科学研究所Melina Schuh及其小组揭示人类卵母细胞纺锤体极组织与不稳定性的机制。该研究于2022年2月11日发表于国际一流学术期刊《科学》。

研究人员发现，NUMA（核有丝分裂器蛋白）介导的微管负极聚集使人类、牛和猪的卵母细胞以及去除了尖顶微管组织中心（aMTOC）的小鼠卵母细胞的主轴极集中。然而，与人类的卵母细胞不同，牛、猪和不含aMTOC的小鼠卵母细胞具有稳定的主轴。

研究人员发现分子马达KIFC1（驱动蛋白超家族蛋白C1）是人类卵母细胞中缺乏的一种稳定主轴的蛋白。KIFC1的耗竭重现了牛和不含aMTOC的小鼠卵母细胞中的纺锤体不稳定，而引入外源KIFC1则挽救了人类卵母细胞中的纺锤体不稳定。因此，KIFC1的缺乏导致了人类卵母细胞的纺锤体不稳定。

据悉，人类卵母细胞容易组装出具有不稳定两极的减数分裂主轴，这可能有利于人类卵子的非整倍体。纺锤体不稳定的根本原因尚不清楚。

附：英文原文

Title: Mechanism of spindle pole organization and instability in human oocytes

Author: Chun So, Katerina Menelaou, Julia Uraji, Katarina Harasimov, Anna M. Steyer, K. Bianka Seres, Jonas Buceviius, Gravydas Lukinaviius, Wiebke Mbius, Claus Sibold, Andreas Tandler-Schneider, Heike Eckel, Rüdiger Moltrecht, Martyn Blayney, Kay Elder, Melina Schuh

Issue&Volume: 2022-02-11

Abstract: Human oocytes are prone to assembling meiotic spindles with unstable poles, which can favor aneuploidy in human eggs. The underlying causes of spindle instability are unknown. We found that NUMA (nuclear mitotic apparatus protein)–mediated clustering of microtubule minus ends focused the spindle poles in human, bovine, and porcine oocytes and in mouse oocytes depleted of acentriolar microtubule-organizing centers (aMTOCs). However, unlike human oocytes, bovine, porcine, and aMTOC-free mouse oocytes have stable spindles. We identified the molecular motor KIFC1 (kinesin superfamily protein C1) as a spindle-stabilizing protein that is deficient in human oocytes. Depletion of KIFC1 recapitulated spindle instability in bovine and aMTOC-free mouse oocytes, and the introduction of exogenous KIFC1 rescued spindle instability in human oocytes. Thus, the deficiency of KIFC1 contributes to spindle instability in human oocytes.

DOI: abj3944

Source: https://www.science.org/doi/10.1126/science.abj3944