ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation.
Tight junctions restrict diffusion of hydrophilic solutes through the paracellular pathways of columnar epithelia. It is now apparent that the barrier function of tight junctions is physiologically regulated. Current models of the tight junction envisage junctional subunits consisting of extracellular "kisses" between plasma membranes of adjacent cells, intramembrane components represented by freeze-fracture fibrils, and cytoplasmic elements of the cytoskeleton. Insights into functional relationships between these various components of tight junctions should be provided by mapping component interrelationships in states of altered junctional permeability. Here we define the spatial distribution of ZO-1 during a state of physiological regulation of intestinal absorptive cell tight junctions. Enhanced permeation of absorptive cell junctions in response to activation of apical membrane Na(+)-solute cotransporters does not lead to redistribution of the ZO-1 pool, as judged from quantitative ultrastructural immunolocalization studies employing two different ZO-1 antibodies. Surprisingly, ZO-1, which normally localizes under junctional kisses/fibrils, focally persists at sites where junctional kisses/fibrils are cleared. These findings suggest that 1) spatial redistribution of ZO-1 does not contribute to physiological regulation of junctions elicited by activation of Na(+)-solute cotransport and 2) ZO-1 and junctional fibrils may spatially dissociate during such regulated states.
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
J L
JL
Madara
S
S
Carlson
J M
JM
Anderson
D000818:Animals; D006224:Cricetinae; D004553:Electric Conductivity / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000502:physiology* / Q000648:ultrastructure; D007421:Intestine, Small; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008647:Mesocricetus; D016253:Microscopy, Immunoelectron; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D014364:Tryptophan; D005947:Glucose