Which of the following proteins is required for the formation of lamellipodia?
Lamellipodium broad veil like extension 1 to 5 micron wide 0.1 to 0.2 micron thick driving mesenchymal migration requires continuous branched actin assembly at leading edge. Key organizer is Rac1 GTP small GTPase activating pentameric WAVE regulatory complex comprising WAVE, Abi, Nap1, Sra1 and HSPC300. Upon activation Rac1 binding to Sra1 releases VCA domain of WAVE which binds G actin and Arp2/3 complex at membrane, inducing nucleation of daughter filaments at 70 degree angle. Iterative branching creates dense network with barbed ends abutting membrane, polymerizing and generating pushing force essential for protrusion. Imaging with photoactivatable actin shows retrograde flow balancing polymerization. Pharmacological inhibition CK666 blocking Arp2/3 activation site abrogates lamellipodia formation, cells instead form filopodia via formins, confirming Arp2/3 indispensability for lamellipodia. Myosin II provides retraction at rear, dynein microtubule motor for centrosome positioning, spectrin supporting membrane cortex, while Arp2/3 specifically drives lamellipodia protrusive network and motility. Continuous turnover of branched meshwork allows rapid adaptation to chemotactic cues and directional persistence during migration.
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Lamellipodia Formation and Arp2/3 Requirement.