Interactions

Direct cell–cell interactions are critical to normal growth and development. In order to build up and maintain different tissue types, cells need to be able to form stable, almost permanent, junctions. But there are also more transient interactions that are essential means of communication between cells.

In order for cells to communicate directly, they must first adhere to another cell. This cell–cell adhesion is a selective process that is dependent on interactions between integral membrane proteins called cell adhesion molecules (CAMs). The CAMs on the surface of one cell can recognise either a different molecule or another CAM on the surface of a second cell and this recognition mediates a transient association between the two cells. An example of CAM-mediated cellular interactions involves the movement of leucocytes (white blood cells) to the site of tissue damage. When tissue damage occurs, leucocytes flock through the circulatory system to the area of damage. They then squeeze through tiny gaps between endothelial cells in the blood vessels in a process referred to as extravasion. For the leucocyte to begin extravasion, it must first bind to an endothelial cell. This is mediated by a class of CAMs known as selectins, which initiate a temporary interaction between leucocytes and the endothelial lining of blood vessels. Selectins in the leucocyte membrane recognise specific carbohydrates on the surface of the endothelial cell, essentially stopping the leucocytes from continued movement in the bloodstream, allowing them to squeeze into the gaps between endothelial cells.

Adherens junctions are more stable interactions between cells, usually involving a specific type of CAM, the cadherins. The cytoskeletons of cells that are destined to adjoin one another in a specific tissue or organ are often joined by cadherins. In these junctions, cadherin proteins are bonded to the actin filaments that make up the cytoskeleton. The extracellular domains of cadherin proteins then interact with cadherin proteins from an adjoining cell, effectively tethering the neighbouring cells together (Fig 13-1).

FIGURE 13-1 Adherens junctions. In one common type of adherens junction, cadherins link to actin filaments and then dimerise with cadherins from adjoining cells to form a stable connection.

[Based on Norman & Lodwick, 2007, The Flesh and Bones of Medical Cell Biology, Mosby]

The activities of cells within an organ or tissue type often need to be tightly regulated. As discussed below, this is often controlled through receptor-mediated extracellular signalling. Adjoining cells, however, are often linked by open channels that allow for rapid cytoplasmic exchange. These gap junctions are transmembrane channels that allow for the diffusion of small molecules between the neighbouring cells (Fig 13-2A). In general, ions—small organic molecules, low-molecular-weight precursors of proteins and nucleic acids—and small signalling molecules can pass through gap junctions whereas proteins and nucleic acids cannot (Fig 13-2B). Cells that are connected by gap junctions are said to be metabolically coupled; in other words, they are nearly identical in terms of electrical and metabolic activity. Gap junctions are made up of connexins, a family of transmembrane proteins, which form a cylinder with an open channel in the centre. This assembly of connexins, the connexon, lines up with a connexon from an adjoining cell to form a continuous channel from one cell to the next.

FIGURE 13-2 Gap junctions. A, Gap junctions consist of assemblies of six connexins, which when adjoining cells align, form an open channel between cells. B, Transport of molecules between cells through gap junctions is limited by the size of the channel. Smaller molecules can pass through the channels, whereas larger molecules are unable to do so.

[Based on Meisenberg & Simmons, 2006, Principles of Medical Biochemistry, 2nd edition, Mosby]

Signalling from a distance

When cells are not in direct connection with one another, communication occurs from a distance. Signalling molecules act by binding to a specific membrane-bound receptor on the target cell. What happens after that interaction occurs depends on the nature of the signalling molecule, of the receptor and of the target cell. But, in general, intercellular signalling involves the following steps:

Synthesis and release of signalling molecules

Systemic changes in the body as a result of environmental changes are mostly controlled by the nervous and endocrine systems. The latter uses hormones as signalling molecules to initiate cellular changes. Hormones range from small peptides, like the insulin and glucagon released by the pancreas, to steroids like testosterone and oestrogen that are made from cholesterol. Hormones are made in signalling cells in endocrine glands and are stored in vesicles. Release of hormones is usually triggered by changes in Ca²⁺ concentration in the signalling cells, which leads to exocytosis of the hormones.

Transport of signalling molecules

Intercellular communication mediated by signalling molecules can be broken down into three general categories—endocrine, paracrine or autocrine signalling. In endocrine signalling, a signalling molecule is released by endocrine organs or glands and moves through the general circulation until it reaches its target cell. This allows for communication from a distance. Most hormones act via endocrine signalling. Paracrine signalling involves a signalling molecule from one cell acting on neighbouring cells, allowing for short distance communication. Autocrine signalling is not, strictly speaking, intercellular communication as it involves a cell responding to signalling molecules that it produces. Cell signalling can also result from signalling molecules that are integral membrane proteins on one cell binding receptors on an adjacent cell (Fig 13-3).

FIGURE 13-3 Signalling from a distance. Endocrine signalling involves hormones that are carried through circulation to their often distant target cells. Paracrine signalling involves a signalling molecule released from one cell acting on nearby cells in the same tissue or organ. In autocrine signalling, a cell both produces and responds to a signalling molecule.

[Based on Voet & Voet, 2005, Biochemistry, 3rd edition, Wiley]

Receptor binding

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