Rho Flares Repair Local Tight Junction Leaks

Abstract

Graphical Abstract Highlights d ZnUMBA is a novel zinc-based ultrasensitive microscopic barrier assay d ZnUMBA detects transient, localized tight junction breaches in developing epithelia d Rho flares rapidly repair tight junctions to minimize leakiness at breach points d Actomyosin-mediated junction contraction promotes tight junction reinforcement

The Leak Pathway: A Pathway in Flux

“…Since these analyses assumed a constant pore length without any independent measurements, these conclusions must be regarded as tentative. We have observed that treatment of MDCK Type II renal epithelial cells with hydrogen peroxide, which increases Leak Pathway permeability, also increases cell twisting and movement (data not shown), similar to the effects of cell division described by Stephenson et al [125]. In this context, it is interesting to note the marked parallels between regulation of tight junction and adherens junction integrity.…”

“…It is likely that these localized regions may not exist on every cell at any single time point. Two recent studies demonstrating a small number of discrete sites where macromolecules cross the tight junction lend strong support for this concept of the Leak Pathway [124,125]. Stephenson et al [125] reported that sites of solute permeation were transient, remaining open for no more than 5 minutes.…”

“…Two recent studies demonstrating a small number of discrete sites where macromolecules cross the tight junction lend strong support for this concept of the Leak Pathway [124,125]. Stephenson et al [125] reported that sites of solute permeation were transient, remaining open for no more than 5 minutes. Richter et al [124] also reported that macromolecule permeability at some sites was transient, being "open" for 30 minutes or less.…”

“…A recent report may provide some insight into the molecular basis for the Leak Pathway and how it may be regulated. Stephenson et al [125] studied the maintenance of tight junctions in the embryonic epithelium of the Xenopus laevis embryo. They demonstrated that localized disruptions of the tight junction occurred at sites of increased tension caused by junction elongation as cells in the embryo divided.…”

Adherens junction serves to generate cryptic lamellipodia required for collective migration of epithelial cells

“…As mentioned already, a hot spot to generate membrane protrusion was multicellular junctions where multiple bicellular junctions meet ( Fig. 2D), and the multicellular junctions are thought to be prone to disruption, as they receive tensile force from the bicellular junctions (Higashi and Miller, 2017;Stephenson et al, 2019). Such force is generated by contraction of junction-associated actomyosin, and therefore we examined whether there is any relation between myosin II activation and clamellipodia formation.…”