Tight junction components

Two principal routes of passive diffusion are recognized transcellular (la —> lb —> lc in Fig. 2.7) and paracellular (2a > 2b > 2c). Lateral exchange of phospholipid components of the inner leaflet of the epithelial bilayer seems possible, mixing simple lipids between the apical and basolateral side. However, whether the membrane lipids in the outer leaflet can diffuse across the tight junction is a point of controversy, and there may be some evidence in favor of it (for some lipids) [63]. In this book, a third passive mechanism, based on lateral diffusion of drug molecules in the outer leaflet of the bilayer (3a > 3b > 3c), wih be hypothesized as a possible mode of transport for polar or charged amphiphilic molecules. 

Many structural components of the tight junctions (TJs) have been defined since 1992 [85-97]. Lutz and Siahaan [95] reviewed the protein structural components of the TJ. Figure 2.7 depicts the occludin protein complex that makes the water pores so restrictive. Freeze-fracture electronmicrographs of the constrictive region of the TJ show net-like arrays of strands (made partly of the cytoskeleton) circumscribing the cell, forming a division between the apical and the basolateral... 

The tight junction is a component of the junctional complexes which join cells. Immediately basolateral to the tight junction is the zonula adherens (Figs. 6 and 7). Because the zonula adherens and the gap junctions are focal contact regions, they do not impact transport by the paracellular pathway. All of these junctions are specialized regions of the lateral cell membrane which demarcate the lateral space. In certain types of cells the lateral space is rather narrow and... 

JM Anderson, BR Stevenson, LA Jesaitis, DA Goodenough, MS Mooseker. (1989). Characterization of ZO-1, a protein component of the tight junction from mouse-liver and Madin-Darby canine kidney cells. J Cell Biol 106 1141-1149. 

Fig. 15.3 D iagram showing a longitudinal cross-section of the blood-brain barrier, with the brain capillary endothelial cells sealed by the tight junctions and surrounded by pericytes and astrocyte foot processes. These cellular components of the BBB are separated by a basement membrane.

Morita K, Furuse M, Fujimoto K, and Tsukita S [1999] Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 96 511-516... 

McCarthy KM, Skare IB, Stankewich MC, Furuse M, Tsukita S, Rogers RA, Lynch RD, and Schneeeberger EE [1996] Occludin is a functional component of the tight junction. J Cell Sci 109 2287-2298... 

Penetration enhancers can show their action by acting either on the membrane components (transcellular mode of action) or on tight junctions (paracellular mode of action) as shown in Figure 25.3. 

Initial attempts at selecting PEs have identified certain surfactants, such as bile salts and fatty acids, which appear to facilitate oligonucleotide absorption. The advantages of these components are many, in that they are endogenous to foods and body constituents, plus the literature is rich with information about the use and exposure of these two classes of compounds [56]. The precise mechanism of action for these PEs is unknown, but is believed to involve a disruption of the mucus layer barrier, an increase in the fluidity of the mucosal membrane, and potentially an opening of the paracellular tight junctions. The mucolytic effect coupled with the increased membrane fluidity imparted by these excipients appears to allow in-... 

Rietveld A, Simons K (1998) The differential miscibility of lipids as basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376 467-479 Saitou M, Furuse M, Saski H, Schulzke JK, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11 4131-4142... 

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