Cell-Cell and Cell-Matrix Adhesion

Cells adhere to each other and to the extracellular matrix through cell surface proteins called cell adhesion molecules (CAMs). Some CAMs are Ca²⁺ dependent whereas others are Ca²⁺ independent.  Adhesion molecules can be divided into four families: (1) immunoglobulin-like adhesion molecules, (2) selectins, (3) cadherins and (4) integrins.

Cadherins are the major CAMs responsible for Ca²⁺ dependent  cell-cell adhesion in vertebrate tissues. There are many types of cadherins which make up the cadherin family and cells in culture can sort themselves out according to the type and level of cadherins they express.  Most cadherins are single pass transmembrane glycoproteins that have a large extracellular part of their polypeptide chain folded into 5 or 6 cadherin repeats. Ca²⁺ ions are positioned between each pair of cadherin repeats. The more Ca²⁺ ions bound, the more rigid the structure.

Selectins arenother major CAM responsible for Ca²⁺ independent cell-cell adhesion are the selectins which are cell surface carbohydrate binding proteins (lectins) which mediate cell-cell adhesion in the bloodstream. For example, L-selectins are found on lymphocytes which recognize oligosaccharides expressed on endothelial cells in lymphoid organs causing the lymphocytes to become trapped. Conversely, at sites of inflammation, endothelial cells switch on expression of selectins which recognize the oligosaccharides on lymphocytes and platelets.

Selectins often work together with a third type of cell adhesion molecule called integrins. Selectins and integrins act in sequence to let lymphocytes leave the bloodstream and enter tissues. The selectins mediate a weak adhesion which allows the white blood cell to roll along the surface of the blood vessel propelled by the flow of blood. This rolling continues until the blood cell activates its integrins (cadherins are not involved in leukocyte recruitment) which causes the cell to bind strongly to the endothelial cell surface and to crawl out of the blood vessel between adjacent endothelial cells.

Integrins

Whereas cadherins, slectins and integrins all depend on extracellular Ca²⁺ to function in cell adhesion, a major CAM which is Ca²⁺ independent are the N-CAMs or "neural cell adhesion molecules" which are expressed in a variety of cells including most nerve cells.

Most cadherins function as transmembrane adhesion proteins that indirectly link the cytoskeleton of the cells they join. This occurs in Cell Junctions like the adherens junctions where the cytoplasmic tails of cadherins interacts indirectly with actin filaments by means of a group of intracellular anchor proteins called "catenins" and with desmosomes where the cytoskeleton is intermediate filaments.

• Occluding junctions: include the tight junctions whose role is particularly prominent in the small intestine where they prevent transport proteins at the apical surface of the epithelia cell (surface facing the lumen) from mixing with those in the basolateral surfaces of the cell. In addition tight junctions insure that spaces between epithelia cells are sealed so that transported molecules cannot diffuse back into the gut. Major transmembrane proteins in a tight junction include the claudins  and occludins.

• Anchoring junctions: connect the cytoskeleton of a cell to the cytoskeleton of other cells using the transmembrane protein cadherin or to the extracellular matrix (basal lamina) through the use of the TM protein integrin. In both cases, there is an intracellular coupling to either actin or intermediate filaments depending on the type of intracellular anchor proteins involved. The various anchoring junctions are contained in the chart below:

• Communicating junctions: include the gap junctions which form channels through transmembrane proteins called connexins. 6 connexins are required to form a channel (called a "connexon") and when the connexons in the PM of 2 cells in contact are aligned, they form a continuous aqueous channel that connects the two cell interiors.