Abstract
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.
Highlights
One of the most striking properties of living cells is their ability to change shape during physiological processes, such as division, migration, and differentiation
Summary Cellular shape is controlled by the submembranous cortex, an actomyosin network mainly generated by two actin nucleators: the Arp2/3 complex and the formin mDia[1]
We show that IQGAP1 controls the activity of the formin mDia[1], Wave regulatory complex (WRC) regulates Arp2/3 branching activity, and SPIN90 mediates an unexpected synergistic action between Arp2/3 and mDia[1]
Summary
One of the most striking properties of living cells is their ability to change shape during physiological processes, such as division, migration, and differentiation. Changes in cortical mechanics can originate from changes in myosin activity[2] or cortex architecture, which arise from changes in actin filament length[3] or network organization[4]. One potential mechanism to control cortex architecture involves regulation of actin nucleators. In vitro, in the presence of profilin, formins generate longer filaments than those created by Arp2/3-mediated branching[5,6] and, in cells, single molecule experiments suggest a similar trend[7]. Actin nucleators generate varied network topologies ranging from highly branched networks generated by the Arp2/3 complex to linear arrays generated by formins and Ena/VASP. Little is known about how nucleator activity is controlled to change network topology and mechanics
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