Cell wound repair requires the coordinated action of linear and branched actin nucleation factors

Abstract

Cells are subjected to a barrage of daily insults that often lead to its cortex being ripped open and requiring immediate repair. An important component of the cell′s repair response is the formation of an actomyosin ring at the wound periphery to mediate its closure. Inhibition of linear actin nucleation factors and myosin result in a disrupted contractile apparatus and delayed wound closure. Here we show that branched actin nucleators function as a scaffold to assemble and maintain this contractile actomyosin cable. Removing branched actin leads to the formation of smaller circular actin-myosin structures at the cell cortex and slow wound closure. Removing linear and branched actin results in failed wound closure. Surprisingly, removal of branched actin and myosin results in the formation of parallel linear actin filaments that undergo a chiral swirling movement to close the wound. These results provide insight into actin organization in contractile actomyosin rings and uncover a new mechanism of wound closure.

Wrangling Actin Assemblies: Actin Ring Dynamics during Cell Wound Repair

“…The presence of ordered branched actin structures is crucial for actin ring formation, as well as its subsequent contraction to effectively close a wound. Indeed, in the absence of branched and linear nucleation promotion factors, no actin structures form [ 60 , 61 ]. In general, WAS family proteins have a one-to-one correspondence with Rho family GTPases (Cdc42 > WASp; Rac > SCAR/WAVE; Rho1 > Wash), where each pair regulates specific dynamic actin organizations.…”

“…However, WAS proteins have recently been shown to have non-redundant roles during cell wound repair. In particular, WASp has a specialized function to regulate the orientation of actin filaments making up the contractile actomyosin ring at wound periphery [ 61 ].…”

“…Although several model organisms share the same groups of recruited proteins, constriction of the assembled actin ring to close the wound can be accomplished through different mechanisms ( Figure 5 ). Several mechanisms have been proposed for actin filament network contractility: (1) sarcomere-like contraction, involving filaments sliding due to motor processivity and crosslinker distribution; (2) actin filament treadmilling, involving continuous actin assembly at the inner edge of the ring and disassembly at the outer ring edge; and (3) F-actin buckling model, involving the mechanical deformation of actin filaments by myosin [ 9 , 25 , 60 , 61 , 80 , 81 ]. However, under certain conditions, cells deficient in one or more of the cytoskeletal components will still attempt to repair wounds.…”

“…However, under certain conditions, cells deficient in one or more of the cytoskeletal components will still attempt to repair wounds. A recent study has demonstrated that a Drosophila embryo lacking the majority of branched actin and myosin exhibits actin filament swirling to close a wound [ 61 ]. Further investigations will be required to uncover the molecular players and pathways underlying new mechanisms of wound closure.…”