Chapter 4 - Regulation of Autophagy by Actin-Associated Signaling Pathways

Abstract

Autophagy mediates the degradation of cytosolic components through a membrane trafficking pathway that delivers cargo to the lysosome. The initiation and maturation stages of autophagy are coupled to elements of the cell cytoskeleton, which provides a structural framework to spatially organize transport and to link extracellular cues with autophagy regulatory pathways. Here, we discuss models showing multiple roles of the actin cytoskeleton and actin-related signaling proteins in the regulation of autophagy, focusing on three major areas. One set of pathways is coordinated by Rho-associated kinases, which control early autophagy initiation events. Multiple members of the myosin superfamily have emerged as critical regulators of early and late stages of autophagy. The actin-nucleation regulatory factor Wiskott–Aldrich syndrome protein and Scar homologue (WASH) regulates a network of ubiquitin modifications on autophagy signaling proteins. Through these actin-associated mechanisms, cells orchestrate the amplitude, and potentially localization, of the autophagy pro-survival pathway.