Bm. Denker et Sk. Nigam, MOLECULAR-STRUCTURE AND ASSEMBLY OF THE TIGHT JUNCTION, American journal of physiology. Renal, fluid and electrolyte physiology, 43(1), 1998, pp. 1-9
Polarized epithelial cells separate two extremely different cellular m
ilieus. The tight junction (TJ) is the most apical component of the ju
nctional complex and serves as the permeability barrier between these
environments. The tight junctional complex appears to be a dynamic and
regulated structure. Some of its protein components have been identif
ied and include the transmembrane protein occludin. Nontransmembrane p
roteins on the cytosolic leaflet including ZO-1, ZO-2, cingulin, 7H6,
and several unidentified phosphoproteins are also believed to be part
of the TJ. Interactions of some of these proteins with the actin cytos
keleton are a major determinant of TJ structure and may also play a ro
le in the regulation of TJ assembly. Recent progress using the ''calci
um switch'' and the ''ATP depletion-repletion'' model of TJ formation
offers new insight regarding how these structures form. TJ biogenesis
appears to be regulated, in part, by classic signal transduction pathw
ays involving heterotrimeric G proteins, release of intracellular Ca2, and activation of protein kinase C. Although many of the details of
the signaling pathways have yet to be defined, these observations may
provide insight into how TJs form during tubular development. Furtherm
ore, it may be possible to suggest potential therapeutic targets for i
ntervention in a variety of diseases (e.g., ischemia, toxic injury to
the kidney and other epithelial tissue) where TJ integrity has been co
mpromised and reassembly is required.