Coupling between apical and paracellular transport processes.
Transcellular transport affects the paracellular flux through 2 distinct mechanisms: by determining the driving force and by altering the permeability of the paracellular pathway. Such coordination ensures efficient transepithelial transport by preventing the build-up of large electrical and osmotic gradients. The regulation of paracellular permeability was originally recognized as increased paracellular flux of water and solutes upon the activation of the intestinal Na+-coupled glucose uptake. Despite great advances in the molecular characterization of the tight junctions that form the structural basis of epithelial barrier functions, the mechanisms whereby apical transporters alter the paracellular pathways remains unresolved. Recent studies suggest that myosin-based contractility is central to this coupling. In this minireview, we summarize our current knowledge of paracellular permeability, its regulation by contractility, and the various signaling events that link apical Na+-glucose cotransport to myosin phosphorylation. While the role of myosin phosphorylation appears to be universal, the mechanism(s) whereby apical transport triggers this process is likely cell specific. The current model suggests that in intestinal cells, a key factor is a p38 MAP kinase-induced Na+/H+-exchanger-mediated alkalinization. We propose an alternative, nonexclusive mechanism in kidney tubular cells, in which the key event may be a Na+-cotransport-triggered plasma membrane depolarization, which in turn leads to Rho-mediated myosin phosphorylation.
Kapus
András
A
The St. Michael's Hospital Research Institute and Department of Surgery, University of Toronto, 30 Bond Street, Queen Wing 7009, Toronto, ON M5B 1W8, Canada.
Szászi
Katalin
K
D001692:Biological Transport / Q000502:physiology*; D001693:Biological Transport, Active / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology*
D018994:Myosin Light Chains; D051269:Sodium-Glucose Transporter 1; D009218:Myosins