The making of a tight junction.
MDCK (epithelial cells from the dog kidney) plated at confluence, establish tight junctions in 12-15 hours through a process that requires protein synthesis, formation of a ring of actin filaments in close contact with the lateral membrane of the cells, calmodulin, and a Ca(2+)-dependent exocytic fusion of tight junction (TJ)-associated components. Monolayers incubated in the absence Ca2+ make no TJs. Yet, if Ca2+ is added under these circumstances, TJs are made with a faster kinetics. Ca2+ is needed mainly at a site located on the outer side of the cell membrane, where it activates uvomorulin and triggers the participation of the cellular components mentioned above, via G-proteins associated with phospholipase C and protein kinase C. In principle, the sites of all these molecules and mechanisms involved in junction formation may be where a variety of agents (hormones, drugs, metabolites) act to produce epithelia with a transepithelial electrical resistance (TER) ranging from 10 to 10,000 omega.cm2. This range may be also due to a variety of substances found in serum and in urine, that increase the TER in a reversible and dose-dependent manner.
Cereijido
M
M
Center for Research and Advanced Studies, México, DF, México.
González-Mariscal
L
L
Contreras
R G
RG
Gallardo
J M
JM
García-Villegas
R
R
Valdés
J
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008561:Membrane Fusion; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D002147:Calmodulin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium