Intercellular junctions are super common, especially between epithelial cells. There are 5 main types, and you should probably know a few of the basics about each.

1. Zonula occludens (tight junction). This is the most apical (closest to the top) of all the cell-cell junctions. It is a super-tight junction – in fact, for a long time, people thought that adjacent membranes were fused together in this junction (they’re not, but they sure look like they are). A few things of note:

• Claudins and occludins are the proteins that form the tight seal between adjacent cell membranes.
• This junction is great for keeping fluids from leaking between cells. If stuff wants to get through, it has to go through the cells, not between. This is a good idea in lots of places, for example, in the gut.
• This junction also establishes “domains” in the cell (apical and basolateral). Cell membrane proteins can move around, but they are restricted to their own domain.

2. Zonula adherens (belt desmosome). Desmo- comes from the Greek word for “bond.” This junction is usually located just below the zonula occludens junction. The membranes are not as closely apposed to each other in this junction (you can see a little space between them).

• Cadherins and catenins are the proteins that provide adhesion between adjacent cells. It’s pretty easy to remember cadherin because this is the zonula adherens junction. It also stands for calcium-dependent adhesion molecule.
• Cadherins and catenins are connected to actin filaments inside the cell. The actin filaments form a nice band around the entire cell that is called the “terminal web” in columnar cells (like those in the intestine).

3. Macula adherens (spot desmosome). This type of junction is super common. There are usually a lot of them, and they act like little spot-welds or rivets between adjacent cells. The combination of the zonula occludens, zonula adherens and macula adherens is called a “junctional complex.”

• Macula means spot (so it’s a nice name choice for this junction).
• The proteins that connect adjacent cells are desmoglein and desmocollin (both of which are cadherins). Desmocollin is a cool name because the -collin part comes from the Greek “kollos” (glue).
• Patients with pemphigus vulgaris make antibodies to desmoglein (which weaken the macula adherens junction, and hence, the connection between epithelial cells). Fluid accumulates between epithelial cells and forms superficial blisters in the skin.
• Desmoglein and desmocollin insert into attachment plaques on the inside of the cell membrane. Cytokeratin filaments inside the cell also attach to these plaques.

4. Gap junction. Unlike all the other junctions, the gap junction is not so much for adhesion, but for allowing ions and other small molecules to pass between cells.

• Can occur anywhere along lateral membrane of cell.
• Common in cardiac muscle cells and ciliated columnar cells (in which you want to innervate cells in a wave-like fashion, with current passing from one cell to the next).
• The actual connecting molecules are called connexons, and they look like little flowers with a hole in the center. Connexons in adjacent cell membranes line up, and stuff flows through the central channel.

5. Hemidesmosome. This is actually not a cell-cell junction, but a cell-basement membrane junction.

• Similar to macula adherens: has an attachment plaque on the inside of the cell membrane, with keratin filaments inside the cell attaching to the plaque.
• Integrins link the attachment plaque to the basal lamina part of the basement membrane.
• Patients with bullous pemphigoid make antibodies to an antigen (“bullous pemphigoid antigen”) within hemidesmosome attachment plaques. Epithelial cells fall away from the basement membrane and fluid accumulates, forming blisters (which are a little deeper than those of pemphigus vulgaris, because they are at the bottom of the epithelium rather than within the epithelium itself).