Mechanisms of actin disassembly

Abstract

The actin cytoskeleton is constantly assembling and disassembling. Cells harness the energy of these turnover dynamics to drive cell motility and organize cytoplasm. Although much is known about how cells control actin polymerization, we do not understand how actin filaments depolymerize inside cells. I briefly describe how the combination of imaging actin filament dynamics in cells and using in vitro biochemistry progressively altered our views of actin depolymerization. I describe why I do not think that the prevailing model of actin filament turnover--cofilin-mediated actin filament severing--can account for actin filament disassembly detected in cells. Finally, I speculate that cells might be able to tune the mechanism of actin depolymerization to meet physiological demands and selectively control the stabilities of different actin arrays.

FIGURE 1:

Alternative modes of actin disassembly. (A) Treadmilling filaments lose actin subunits from the pointed ends of filaments. Pure actin treadmills at steady state, which is a popular model for describing actin turnover in cells. (B) Dynamic instability would occur if ATP hydrolysis were to convert the barbed end from one that grows to one that shrinks. Microtubules and prokaryotic ParM filaments undergo dynamic instability, but dynamic instability has not been seen with actin. (C) Severing cuts a filament to produce two daughter filaments without loss of polymer mass. Cofilin severs actin filaments in vitro. (D) Whole-filament destabilization proposes a highly cooperative process in which long stretches of polymer abruptly convert to monomer. Whole-filament destabilization might describe actin disassembly in the presence of cofilin, coronin, and Aip1.