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W2. GM 19-Oct “Approaches to the Developmental Biology” - Chapters 3, 4, 5 (Celi adhesion molecules/ECM)

Celi adhesion molecules //problem of the day//

Organisms are not just bags of cells, rather each tissue has a definite cellular composition and microarchitecture. This is determined partly by the cell-surface molecules by which cells interact with each other, and partly by the components of the extracellular matrix (ECM). Virtually all proteins on the celi surface or in the ECM are glycoproteins, containing oligosaccharide groups added in the endoplasmic reticulum or Golgi apparatus after translation and before secretion from the celi.

■    carbohydrate groups often have rather little effect on the biological activity of the protein but they may affect its physical properties and stability. ‘

Cells are attached to each other by adhesion molecules:

'T cadherins - which stick cells together in the presence of Ca, celi adhesion molecules (CAMs) - do not reąuire Ca ■S integrins - attach cells to the extracellular matrix When cells come together they often form gap junctions at the region of contact - they consist of smali pores joining the cytosol of the two cells, connexons, are assembled from proteins called connexins.

Cadherins

Family of single-pass transmembrane glycoproteins which can adhere tightly to similar molecules on other cells in the presence of calcium.

Cadherins are the main factors attaching embryonic cells together.

which is why embryonic tissues can often be caused to disaggregate simply by removal of calcium.

■    The cytoplasmic taił of cadherins is anchored to actin bundles in the cytoskeleton by a complex including proteins called catenins

° (3-catenin, is also a component of the Wnt signalling pathway, providing a potential link between celi signalling and celi association.

Cadherins were first named for the tissues in which they were originally found, so E-cadherin (epithelia) and N-cadherin (neural tissue).

Immunoglobulin superfamily

Single-pass transmembrane glycoproteins with a number of disulfide-bonded loops on the extracellular region, similar to the loops found in antibody molecules. They also bind to similar molecules on other cells, but unlike the cadherins they do not need calcium to do so.

■    The neural celi adhesion molecule (NCAM) is composed of a large family of different proteins formed by alternative splicing. It may carry a large amount of polysialic acid on the extracellular domain, and this can inhibit celi attachment because of the repulsion between the concentrations of negative charge on the two cells. Related molecules include LI and ICAM (intercellular celi adhesion molecule).

Integrins

Cell-surface glycoproteins that interact mainly with components of the extracellular matrix. They are heterodimers of a- and p-subunits, and reąuire either magnesami or calcium for binding. There are numerous different a and p-chain types and so there is a very large number of potential heterodimers. Integrins are attached by their cytoplasmic domains to microfilament bundles, so, like cadherins, they provide a link between the outside world and the cytoskeleton. They are also thought on occasion to be