Autophagy in adhesion and migration

Abstract

Autophagy, a pathway for lysosomal-mediated cellular degradation, has recently been described as a regulator of cell migration. Although the molecular mechanisms underlying autophagy-dependent motility are only beginning to emerge, new work demonstrates that selective autophagy mediated by the autophagy cargo receptor, NBR1, specifically promotes the dynamic turnover of integrin-based focal adhesion sites during motility. Here, we discuss the detailed mechanisms through which NBR1-dependent selective autophagy supports focal adhesion remodeling, and we describe the interconnections between this pathway and other established regulators of focal adhesion turnover, such as microtubules. We also highlight studies that examine the contribution of autophagy to selective degradation of proteins that mediate cellular tension and to integrin trafficking; these findings hint at further roles for autophagy in supporting adhesion and migration. Given the recently appreciated importance of selective autophagy in diverse cellular processes, we propose that further investigation into autophagy-mediated focal adhesion turnover will not only shed light onto how focal adhesions are regulated but will also unveil new mechanisms regulating selective autophagy.

Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

“…Autophagy is not only a simple tool for the elimination of cellular materials, but is also an important recycling system for tissue renovation [29-31]. Recently, the role of autophagy in bone physiology and pathophysiology has gradually been unmasked.…”

The Interconnections between Autophagy and Integrin-Mediated Cell Adhesion

“…As such, focal adhesions comprise both scaffolding and signaling proteins organized into functional layers that link cytoplasmic portions of integrins to signaling and adaptor molecules and facilitate the transmission of forces via interactions with cytoskeletal elements (Figure 4) [6, 7]. Focal adhesions are highly dynamic and the balance of assembly to disassembly from the ECM is often altered in metastatic cancer cells that must detach, undergo migration, and re-reattach at the metastatic site [83]. …”

“…A number of signaling mechanisms also regulate the disassembly of focal adhesions, and recently, autophagy has been implicated as a key mediator of this process by targeting directly focal adhesion proteins for degradation (Figure 4) [83]. Phosphorylation of PAX by Src has been shown to promote its interaction with the autophagosome associated LC3 proteins and subsequent autophagic degradation leading to focal adhesion disassembly [12].…”

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

“…Moreover, components of the autophagic apparatus have recently been shown to participate in processes other than the degradation of cytoplasmic material. These processes include: LC3-associated phagocytosis (LAP) 10 (BOX 2), migration (mainly as a result of focal adhesion turnover) 11 and unconventional secretion, which is a mechanism by which cytoplasmic entities (including soluble proteins, organellar material and pathogens) are exported from the cell in a manner that does not depend on the conventional secretory route that operates between the endoplasmic reticulum and the Golgi apparatus 12 .…”