Role of autophagy in the regulation of epithelial cell junctions

Abstract

Autophagy is a cell survival mechanism by which bulk cytoplasmic material, including soluble macromolecules and organelles, is targeted for lysosomal degradation. The role of autophagy in diverse cellular processes such as metabolic stress, neurodegeneration, cancer, aging, immunity, and inflammatory diseases is being increasingly recognized. Epithelial cell junctions play an integral role in the cell homeostasis via physical binding, regulating paracellular pathways, integrating extracellular cues into intracellular signaling, and cell-cell communication. Recent data indicates that cell junction composition is very dynamic. The junctional protein complexes are actively regulated in response to various intra- and extra-cellular clues by intracellular trafficking and degradation pathways. This review discusses the recent and emerging information on how autophagy regulates various epithelial cell junctions. The knowledge of autophagy regulation of epithelial junctions will provide further rationale for targeting autophagy in a wide variety of human disease conditions.

Keywords: adherens junction; autophagy; endocytosis; gap junction; inflammatory bowel disease; tight junction.

Figure 1.

Autophagy enhances the epithelial barrier function. Filter-grown intestinal Caco-2 monolayers were incubated in starvation medium (Earle's balanced salt solution) to induce autophagy. Starvation significantly increased transepithelial resistance (TER) and progressively reduced urea flux (^#, *, p < 0.01 vs. time 0). Adapted from Nighot et. al., 2015.

Figure 2.

Summary of the cell homeostatic effects of autophagy on the epithelial cell junctions. Various positive or inhibitory regulators of authophagic effects on cell junctions are listed. The backdrop shows transmission electron micrograph of mouse small intestinal tight junction and adherens junction.