Volume 29, No 8, Aug 2019
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 29 Issue 8, August 2019: 666-679
ORIGINAL ARTICLES
NDP52 tunes cortical actin interaction with astral microtubules for accurate spindle orientation
Huijuan Yu 1,2 , Fengrui Yang 1,3, Peng Dong4, Shanhui Liao1, Wei R. Liu 1,2 , Gangyin Zhao 1,2 , Bo Qin 1,2 , Zhen Dou 2,3 , Zhe Liu4, Wei Liu5,Jianye Zang 1,3 , Jennifer Lippincott-Schwartz4, Xing Liu 1,2,3 and Xuebiao Yao 1,2,3
1Hefei National Center for Physical Sciences at the Microscale & CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230026,China; 2Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, Hefei 230026 Anhui, China; 3MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei 230027 Anhui, China; 4Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA 20147, USA and 5 Zhejiang University School of Medicine, Hangzhou 310058 Zhejiang, China
Correspondence: Xuebiao Yao (yaoxb@ustc.edu.cn)
Oriented cell divisions are controlled by a conserved molecular cascade involving Gαi, LGN, and NuMA. Here, we show that NDP52 regulates spindle orientation via remodeling the polar cortical actin cytoskeleton. siRNA-mediated NDP52 suppression surprisingly revealed a ring-like compact subcortical F-actin architecture surrounding the spindle in prophase/prometaphase cells, which resulted in severe defects of astral microtubule growth and an aberrant spindle orientation. Remarkably, NDP52 recruited the actin assembly factor N-WASP and regulated the dynamics of the subcortical F-actin ring in mitotic cells. Mechanistically, NDP52 was found to bind to phosphatidic acid-containing vesicles, which absorbed cytoplasmic N-WASP to regulate local filamentous actin growth at the polar cortex. Our TIRFM analyses revealed that NDP52-containing vesicles anchored N-WASP and shortened the length of actin filaments in vitro. Based on these results we propose that NDP52-containing vesicles regulate cortical actin dynamics through N-WASP to accomplish a spatiotemporal regulation between astral microtubules and the actin network for proper spindle orientation and precise chromosome segregation. In this way, intracellular vesicles cooperate with microtubules and actin filaments to regulate proper mitotic progression. Since NDP52 is absent from yeast, we reason that metazoans have evolved an elaborate spindle positioning machinery to ensure accurate chromosome segregation in mitosis.
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