Key result
Knockout of WAVE1 and WAVE2 in B16-F1 melanoma cells demonstrated redundant roles in lamellipodia formation but distinct roles in controlling actin network extension.
Why the study?
It remained unclear whether WAVE1 and WAVE2 perform similar or distinct roles at the leading edge, with conflicting reports regarding Arp2/3-independent activities of WAVE1 on actin filament elongation.
WAVE1 and WAVE2 have redundant roles in lamellipodia formation but distinct roles in controlling actin network extension at the leading edge.
WAVE isoform data from animal models warrant no clinical extrapolation; leaves open distinct actin extension mechanisms for mechanistic follow-up.
SCAR/WAVE proteins and Arp2/3 complex assemble branched actin networks at the leading edge. Two isoforms of SCAR/WAVE, WAVE1 and WAVE2, reside at the leading edge, yet it has remained unclear whether they perform similar or distinct roles. Further, there have been conflicting reports about the Arp2/3-independent biochemical activities of WAVE1 on actin filament elongation. To investigate this in vivo, we knocked out WAVE1 and WAVE2 genes, individually and together, in B16-F1 melanoma cells. We demonstrate that WAVE1 and WAVE2 are redundant for lamellipodia formation and motility. However, there is a significant decrease in the rate of leading edge actin extension in WAVE2 KO cells, and an increase in WAVE1 KO cells. The faster rates of actin extension in WAVE1 KO cells are offset by faster retrograde flow, and therefore do not translate into faster lamellipodium protrusion. Thus, WAVE1 restricts the rate of actin extension at the leading edge, and appears to couple actin networks to the membrane to drive protrusion. Overall, these results suggest that WAVE1 and WAVE2 have redundant roles in promoting Arp2/3-dependent actin nucleation and lamellipodia formation, but distinct roles in controlling actin network extension and harnessing network growth to cell protrusion.
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Tang et al. (2020) studied this question. Knockout of WAVE1 and WAVE2 genes was evaluated on Lamellipodia formation, motility, and rate of leading edge actin extension. Knockout of WAVE1 and WAVE2 in B16-F1 melanoma cells demonstrated redundant roles in lamellipodia formation but distinct roles in controlling actin network extension.
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