SCAR/WAVE is activated at mitosis and drives myosin-independent cytokinesis

被引:40
作者
King, Jason S. [1 ]
Veltman, Douwe M. [1 ]
Georgiou, Marios [2 ]
Baum, Buzz [2 ]
Insall, Robert H. [1 ]
机构
[1] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland
[2] UCL, MRC LMCB, London WC1E 6BT, England
基金
英国医学研究理事会;
关键词
Dictyostelium; SCAR/WAVE; Cytokinesis; DICTYOSTELIUM-DISCOIDEUM; CELL MOTILITY; ACTIN CYTOSKELETON; SHAPE CHANGES; PROTEIN; SCAR; DROSOPHILA; ADHESION; SPINDLE; DIVISION;
D O I
10.1242/jcs.063735
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cell division requires the tight coordination of multiple cytoskeletal pathways. The best understood of these involves myosin-II-dependent constriction around the cell equator, but both Dictyostelium and mammalian cells also use a parallel, adhesion-dependent mechanism to generate furrows. We show that the actin nucleation factor SCAR/WAVE is strongly activated during Dictyostelium cytokinesis. This activation localises to large polar protrusions, driving separation of the daughter cells. This continues for 10 minutes after division before the daughter cells revert to normal random motility, indicating that this is a tightly regulated process. We demonstrate that SCAR activity is essential to drive myosin-II-independent cytokinesis, and stabilises the furrow, ensuring symmetrical division. SCAR is also responsible for the generation of MiDASes, mitosis-specific actin-rich adhesions. Loss of SCAR in both Dictyostelium and Drosophila leads to a similar mitotic phenotype, with severe mitotic blebbing, indicating conserved functionality. We also find that the microtubule end-binding protein EB1 is required to restrict SCAR localisation and direct migration. EB1-null cells also exhibit decreased adhesion during mitosis. Our data reveal a spindle-directed signalling pathway that regulates SCAR activity, migration and adhesion at mitosis.
引用
收藏
页码:2246 / 2255
页数:10
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