期刊
NATURE CELL BIOLOGY
卷 22, 期 7, 页码 803-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-020-0531-y
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资金
- Human Frontier Science Program Young Investigator grants [RGY66/2013]
- Medical Research Council UK (Medical Research Council programme award) [MC_UU_12018/5]
- European Research Council [StG-679116, CoG-647186]
- Biotechnology and Biological Sciences Research Council [BB/R00627, BB/R000042]
- Fondation pour la Recherche Medicale [DEI 20151234415]
- Agence Nationale de la Recherche
- Canadian Institute of Health Research [MOP-142374]
- Fonds de recherche du Quebec-Sante Senior Investigator Career Award
- France-BioImaging [ANR10-INBS-04]
- MRC [MC_UU_12018/5, MC_UU_00012/5] Funding Source: UKRI
Cell shape is controlled by the submembranous cortex, an actomyosin network mainly generated by two actin nucleators: the Arp2/3 complex and the formin mDia1. Changes in relative nucleator activity may alter cortical organization, mechanics and cell shape. Here we investigate how nucleation-promoting factors mediate interactions between nucleators. In vitro, the nucleation-promoting factor SPIN90 promotes formation of unbranched filaments by Arp2/3, a process thought to provide the initial filament for generation of dendritic networks. Paradoxically, in cells, SPIN90 appears to favour a formin-dominated cortex. Our in vitro experiments reveal that this feature stems mainly from two mechanisms: efficient recruitment of mDia1 to SPIN90-Arp2/3 nucleated filaments and formation of a ternary SPIN90-Arp2/3-mDia1 complex that greatly enhances filament nucleation. Both mechanisms yield rapidly elongating filaments with mDia1 at their barbed ends and SPIN90-Arp2/3 at their pointed ends. Thus, in networks, SPIN90 lowers branching densities and increases the proportion of long filaments elongated by mDia1. Cao et al. show that SPIN90 enhances formation of Arp2/3-mediated unbranched filaments and promotes a formin-based cortex by recruiting mDia1 or forming a ternary SPIN90-Arp2/3-mDia1 complex.
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