Cytoplasmic regulation of tight-junction permeability: effect of plant cytokinins

Abstract

The significance of the "leaky" tight junction might be understood better if cells of the epithelial monolayer possessed mechanisms to regulate molecular flow through the junction. To test this possibility, Necturus gallbladder, a representative leaky epithelium, was studied before, during, and after mucosal exposure to plant cytokinins and two other microfilament-active drugs, cytochalasin B and phalloidin. Concomitant with morphological changes in microfilaments, cytokinins induced rapid reversible increases in transepithelial resistance and potential difference (PD) and decreases in NaCl dilution potentials, with no change in the ratio of relative cell membrane resistances. Cytochalasin B (0.2-1.2 microM) and phalloidin (0.6-12.7 microM) caused similar changes in transepithelial resistance and PD. When the intramembranous structure of tight junctions was studied by freeze fracture, peak cytokinin-induced increments in transepithelial resistance were associated with more disorder in the strand meshwork resulting in a small increase in tight junction depth, but there was no evidence of de novo strand assembly. These studies suggest that permeability of the tight junction of Necturus gallbladder is subject to rapid reversible modulation, possibly under cytoskeletal control.

Contribution of F-Actin to Barrier Properties of the Blood-Joint Pathway

“…This conclusion is in keeping with the view that intercellular junction proteins, such as the cadherin-catenin complex, are restrained spatially by linkage through ␣-actinin to the actin cytoskeleton (12). Other cell lines with a similar junctional biochemistry show a reduction in the number of junctional strands after cytochalasin treatment (4,34,42). Our observations do not exclude the formation of transcellular gaps, as opposed to intercellular gaps (37), or the involvement of vesicular-vacuolar organelles (17).…”

Effects of polycations on pulmonary vascular permeability in conscious sheep.

“…The precise mechanism of macromolecular transport across the plasma-lymph barrier is controversial. One proposed mechanism is endothelial contraction, which results in opening of leaky sites and thus increased protein permeability (33)(34)(35). It has been reported that endothelial contraction is mediated by transformation of intracellular microfilaments, the magnitude of which may be dependent on intracellular cAMP and/or calcium levels (13)(14)(15).…”

Molecular Basis of Epithelial Barrier Regulation

“…22,23 Moreover, functional studies showed that fungal-derived cytochalasins, which sever actin filaments, were able to disrupt tight junction barrier function and structure. 24 Although one might conclude from these data that tight junctions needed supporting actin filaments to maintain their structural, and therefore functional, integrity, the observation that cytochalasin-induced tight junction disruption was energy-dependent appeared to refute that interpretation. 25 Rather, ultrastructural examination showed that cytochalasin caused the morphological condensation of perijunctional actin, 25 suggesting that cytochalasin-induced severing of actin filaments might cause cytoskeletal contraction that, in turn, led to tight junction disruption.…”