2. What are Tight Junctions
Tight junctions form the continuous
intercellular barrier between epithelial
cells, which is required to separate tissue
spaces and regulate selective movement
of solutes across the epithelium.
3. Structure of Tight junctions
The portion of the cell exposed to the lumen is called its
apical surface.
The rest of the cell (i.e., its sides and base) make up the
basolateral surface.
Tight junctions seal adjacent epithelial cells in a
narrow band just beneath their apical surface. They
consist of a network of claudins and other proteins.
4. Functions of Tight
Junctions
Tight junctions perform two vital functions:
● They limit the passage of molecules and
ions through the space between cells. So
most materials must actually enter the cells
(by diffusion or active transport) in order to
pass through the tissue. This pathway
provides tighter control over what
substances are allowed through.
5. ● They block the movement of integral membrane
proteins (red and green ovals) between the apical
and basolateral surfaces of the cell. Thus the
special functions of each surface, for example
○ receptor-mediated endocytosis at the apical
surface
○ exocytosis at the basolateral surface can be
preserved.
Exocytosis is the reverse of endocytosis.
And that is just as well. In 30 minutes an active cell like a
macrophage (right) can endocytose an amount of plasma
membrane equal to its complete plasma membrane.
6. Receptor mediated Endocytosis
Some of the integral membrane proteins that a cell displays at
its surface are receptors for particular components of the ECF
(extracellular Fluid). For example, iron is transported in the
blood complexed to a protein called transferrin. Cells have
receptors for transferrin on their surface. When these receptors
encounter a molecule of transferrin, they bind tightly to it. The
complex of transferrin and its receptor is then engulfed by
endocytosis. Ultimately, the iron is released into the cytosol.
The strong affinity of the transferrin receptor for transferrin (its
ligand) ensures that the cell will get all the iron it needs even if
transferrin represents only a small fraction of the protein
molecules present in the ECF. (Extracellular Fluid)
7. Pathway of tight junctions
Transcellular transport involves the transportation of
solutes by a cell through a cell.In contrast,
paracellular transport is the transfer of substances
across an epithelium by passing through an
intercellular space between the cells. . Paracellular
permeability can be divided into two distinct
pathways, the Pore Pathway mediating the
movement of small ions and solutes and the Leak
Pathway mediating the movement of large solutes.
Paracellular permeability barrier- Claudin protein.
Leak permeability barrier-Occludin, Zo protein,
Tricellulin and actin.
8. where would we find these tight junctions
Tight junctions are located within our
body's epithelia. Epithelia is the plural
of epithelium. Epithelium is a word
that refers to the covering of the
body's internal and external surfaces.
This includes organs (such as skin),
blood vessels and body cavities.
9. How this information might be relevant to a future healthcare practitioner
Tight junctions is crucial to protect the body against stress stimuli related to
inflammation and infection. In Skin under homeostatic conditions efficiently protects
and/or minimizes damage from both environmental (e.g. microorganisms, physical
trauma, ultraviolet radiation) and endogenous (e.g., cancers, inflammation) factors.
And in Intestinal epithelia the tight junctions (TJs) are essential to the function of the
physical intestinal barrier, regulating the paracellular movement of various substances
including ions, solutes, and water across the intestinal epithelium. Tight junctions contains
number of protein like claudins , occludin etc which play a critical role in regulating TJ
barrier function. So the tight junctions dysfunction may interfere with the protein
expression causing pathogenesis of a number of intestinal and common cutaneous
inflammatory and neoplastic conditions. So understanding the role of tight junctions may
help to play a vital role in diagnosing many intestinal and skin conditions in the future.
10. What diseases or conditions can affect tight junctions?
Barrier dysfunction includes increased paracellular permeability resulting from enhanced flux
across the tight junction, but may also be caused by epithelial damage, including apoptosis,
erosion, and ulceration. Studies reveal that TJ dysfunction is closely related to inflammatory
and metabolic disorders including Inflammatory Bowel Disease, Non alcoholic fatty
liver,Non-alcoholic Steatohepatitis, and obesity via the disruption of TJ barrier functions.
Thus, the maintenance of TJ integrity is likely a good strategy to prevent and/or treat these
diseases. And in Crohn's disease (CD) and ulcerative colitis (UC) share common features
such as epithelial breaks, a reduction in tight junction strands, and glandular atrophy. Then
Mutations in the claudin14 and the claudin16 genes (proteins of tight junctions) result in
hereditary deafness and hereditary hypomagnesemia.
11. References
Anderson, J. M., & Van Itallie, C. M. (2009). Physiology and function of the tight junction. Cold Spring
Harbor perspectives in biology, 1(2), a002584. https://doi.org/10.1101/cshperspect.a002584
Brandner, J. M., Zorn-Kruppa, M., Yoshida, T., Moll, I., Beck, L. A., & De Benedetto, A. (2015). Epidermal tight junctions in
health and disease. Tissue barriers, 3(1-2), e974451. https://doi.org/10.4161/21688370.2014.974451
Lee, B., Moon, K. M., & Kim, C. Y. (2018). Tight Junction in the Intestinal Epithelium: Its Association with Diseases and
Regulation by Phytochemicals. Journal of immunology research, 2018, 2645465. https://doi.org/10.1155/2018/2645465
Sawada N. (2013). Tight junction-related human diseases. Pathology international, 63(1), 1–12.
https://doi.org/10.1111/pin.12021
Shen, L., Weber, C. R., Raleigh, D. R., Yu, D., & Turner, J. R. (2011). Tight junction pore and leak pathways: a dynamic
duo. Annual review of physiology, 73, 283–309. https://doi.org/10.1146/annurev-physiol-012110-142150