Regulation of epithelial permeability by the actin cytoskeleton

Abstract

The actin cytoskeleton is a dynamic structure necessary for cell and tissue organization, including the maintenance of epithelial barriers. The epithelial barrier regulates the movement of ions, macromolecules, immune cells and pathogens, and is thus essential for normal organ function. Disruption in the epithelial barrier has been shown to coincide with alterations of the actin cytoskeleton in several disease states. These disruptions primarily manifest as increased movement through the paracellular space, which is normally regulated by tight junctions. Despite extensive research demonstrating a direct link between the actin cytoskeleton and epithelial permeability, our understanding of the physiological mechanisms that link permeability and tight junction structure are still limited. In this review we explore the role of the actin cytoskeleton at tight junctions and present several areas for future study.

Knockout Mice Reveal Key Roles for Claudin 18 in Alveolar Barrier Properties and Fluid Homeostasis

“…Expression of occludin, believed to be important in regulating TJ solute permeability (43) The F-actin cytoskeleton is closely associated with TJs and plays a critical role in regulating structural and functional properties of apical cell junctions (44). Despite this known interdependence, precise molecular interactions that serve to stabilize the connection between the cytoskeleton and TJ proteins are poorly understood (37).…”

The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks

“…Tight junctions of epithelial and endothelial cells form charge-and size-selective barriers that regulate the paracellular movement of ions and solutes (1,2) and function in cell polarity (3) and cytoskeletal regulation (4). To date, about 40 proteins have been localized to the tight junction (5), but identification approaches have not been systematic, and the list is likely to be incomplete.…”

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

“…as it connects the apical F-actin scaffold to membrane proteins in the apical brush border of intestinal cells. E-cadherin, a cell adhesion molecule normally found in the lateral membrane of these cells, represents one of the prime mediators of intercellular adhesion and is therefore a classic marker of intestinal barrier integrity (16,17). Our experiments using Triton-extraction provide direct evidence for cytoskeletal disruption, due to the fact that both marker proteins dissociate from their cytoskeletal anchorage into the Triton soluble fraction upon gliadin exposure.…”

“…Distinct morphological alterations related to cytoskeletal disruption have been described in CD, like the finding of substantially reduced numbers of cellular microvilli or the widening of intercellular gaps (13,35,36). In this regard, ezrin and E-cadherin represent attractive markers of cytoskeletal disruption and altered barrier integrity (17,37). Ezrin is known as a typical marker protein of cytoskeletal disruption, Aliquots of cytoskeletal pellets obtained immediately after gliadin exposure (I-Pel) are resuspended either in their own Hsp70 lacking supernatant (I-Sup), or in the supernatant of control group, also containing no Hsp70 (C-Sup), or in Hsp70 rich supernatant (R-Sup) isolated following recovery from gliadin exposure.…”

“…Gliadin also alters expression of junctional proteins, for example, ezrin or E-cadherin, which are involved in the barrier function of the intestinal epithelium (8,(13)(14)(15). The actin cytoskeleton network of the enterocyte is known to maintain its integrity by its direct interaction with the tight and adherens junction proteins (16)(17)(18). Ezrin serves as an intermediate between the actin cytoskeleton and the cytoplasmic membrane of cells.…”