This website was developed by undergraduate biology researchers working with Dr. Karen Bernd at Davidson College.

Tight Junctions (and other cellular connections)

Types of Junctions

There are four major types of junctions in epithelial cells. Some encircle the cell like a belt, attaching it to it's neighbors on all sides. Others are more like 'spot welds' that tie two cells together at a specific region or form a tunnel connecting the cytoplasm of adjacent cells.

1) Tight Junctions form the closest contact between adjacent cells known in nature. Found in the apical region around the cell's circumference.

2) Desmosomes serve localized adhesive function and connect the plasma membrane to intermediate filaments in the cytoplasm. The connections are especially important in stratified epithelium.

3) Gap junctions consist of intercellular channels in the plasma membrane of adjacent cells. Small molecules can diffuse across the channel and into the cytoplasm of the other cell.

4) Adherens junctions play a role in intracellular adhesion and the interaction of the actomyosin cytoskeleton with the plasma membrane.

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Figure 1. Tight junctions, desmosomes, gap junctions, and adherens junctions (not depicted here) are present in all epithelial cells along the lateral surface.














Introduction to Tight Junctions- What are they?

Tight junctions are multiprotein complexes that mediate cell-cell adhesion and regulate transportation through the extra-cellular matrix. (See transcytosis for more information on intra-cellular transport.) A defining feature of epithelial cells, tight junctions are found in no other cell type.

Because tight junctions encircle the cell and attach it tightly to its neighbors, these junctions act as a barrier preventing molecules from diffusing across an epithelial sheet between adjacent cells. When situations occur where molecules need get through the layer (in the gap indicated by 'paracellular signaling' in Figure 2) their transport is a multi-step process, involving several signal pathways, regulation of junction proteins, and alternations in cytoskeletal organization. Tight junctions are a major regulator of permeability, expressing different levels of "tightness" based on location and chemical stimuli. The 'looser' the connection, the greater the variety of molecules that can get across the epithelial sheet.

Transmembrane proteins of the tight junctions are responsive to glycoprotein immunoglobin G (IgG) from cells and to surface antigens on bacteria. Binding of these molecules act as chemical stimuli regulating the tightness of the connections. Recognizing these particular molecules is important becauseof the role signaling plays in the secondary immune response.





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Figure 2. Tight junctions are regulated by multiple signaling pathways in a multistep process. This figure depicts the complexity of protein interactions between tight junctions.


Functions of Tight Junctions within Epithelial Cells
  • Barrier and fence function
    • Tight junctions act as one type of specialized intercellular junctional complex that mediates transport of molecules between cells, deemed the barrier function.
    • Tight junctions also help to distinguish the apical and basolateral domains of the cell by acting as intracellular barriers to macromolecules and proteins between these two regions.
  • Regulation of cell polarity
    • Tight junctions maintain apico-basal polarity via protein complexes (CRB3 and Par3 complexes). Cell polarity is also believed to be regulated via second-messenger hormone pathways and PKC/PKA pathways, which increase permeability to calcium and chlorine ions.


Three main transmembrane protein families are found in tight junctions; members of the occludin, claudins, and junctional adhesion molecules (JAMs) familes.

1) Occludin proteins consist of 4 domains- 2 intracellular and 2 extracellular and are involved with the regulation of signaling event.

2) Claudins proteins compose the major structural and functional elements of tight junctions. They also consist of 4 domains- 2 intracellular and 2 extracellular and mediate calcium-independent cell-cell adhesion.

3) JAMs have only a single transmembrane domain, unlike occludin and claudins. While JAM proteins are believed to regulate the paracellular barrier, direct evidence is lacking to support this.

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Figure 3. Tight junctions are composed of three main protein families.

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Figure 4. Transmembrane proteins form complexes at connecting
points called kissing points.


Epithelial cells differentiate during the 8-cell embryonic stage immediately before gastrulation. Formation begins with a signal cascade that results in the production of tight junction proteins, including occludin proteins and claudins proteins. These transmembrane proteins protrude from the cell and begin to expand towards adjacent epithelial cells. As proteins from adjacent cells near each other, attractive interactions draw proteins together to form a complex quaternary structure. Tight junctions form some of the strongest and closest associations between cells discovered thus far. Even upon cell death, tight junctions do not disjoin but remain attached until the dead cell is replaced.

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Figure 5. Transmembrane proteins form a paracellular structure.


Balda, M.S., Fallon, M.B., Van Itallie, C.M., Anderson, J.M. 1992. “Structure, Regulation, and Pathophysiology of Tight Junctions in the Gastrointestinal Tract.” The Yale journal of Biology and Medicine 65: 725-735.

Fanning, A.S., Mitic, L.L, Anderson, J.M. 1999. "Transmembrane Proteins in the Tight Junction Barrier." J Am Soc Nephrol 10: 1337-1345.

Hill, M. (2009). Cell junctions.

Liu, Z., Li, N., Neu, J. 2005. "Tight junctions, leaky intestines, and pediatric diseases." Acta Pediatrica 94: 386-393.

SABiosciences.Pathway Central: Epithelial Tight Junctions.2006. 02 Oct 2010.

Shin, K., Fogg, V., & Margolis, B. (2006). Tight junctions and cell polarity. Annual Review of Cell and Developmental Biology, (22), 207.

Signal transduction education.

Tang Biology Direct 2006 1:37. 02 October 2010.

Yu, Q., Yang, Q. 2009. “Diversity of tight junctions between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier.” Cell Biology International 33: 78-82.

Zivkovic, B. Cell-cell interactions.


Send comments, concerns or questions to Dr. Karen Bernd