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how does a body respond to changes in the surrounding environment, like a rise in temperature, for example? 'Messages' about the change in physical/ chemical conditions are conveyed to the body through various 'agents'. These messages are conveyed to genes, which control all body functions. The genes can be switched on or off through genetic mechanisms in which calcium molecules have a vital role to play. But how are these messages conveyed to a cell? Not much is known about this.

Some recent findings have improved our understanding of how living cells receive signals. Researchers increasingly are finding that communication between the external environment and the living cell is through the calcium ion. Typically, the sensory molecules (known as receptors) on the surface of the cell are stimulated by a change in the intensity of some signal.The signal is conveyed to the interior of the cell because the receptors are partly inside the cell and partly outside it. Until recently, that is.

Thereafter, other signalling agents come into play. These cause a temporary increase in the level of calcium within the cell, either by 'pulling in' calcium from the outside, or by inducing the release of calcium from stores inside the cell, or both. The increased calcium, in turn, causes the expression of certain genes. The details of this last step have been unclear.

Angel Carrin and colleagues at the Institute of Neurobiology in Madrid, Spain, have now taken the first step towards a long-sought goal by discovering a protein that binds specifically to calcium and represses the activity of a certain gene. The gene, which in humans appears to influence both the acquiring of memory and pain, is regulated through part of its dna sequence known as the "downstream regulatory" sequence, or dre .

This sequence plays the role of a silencer -- it represses the activity of the gene. For the expression of the gene, the normal state of repression has to be reversed at the dre sequence. The newly identified protein regulates the activity of dre by antagonising its activity, and is known as a transcriptional repressor or 'antagonist modulator' ( am for short). All of which makes for the happy acronym dream to describe the protein's function ( Nature , Vol 398, No 6722).

The approach used by Carrin and her colleagues was to try and identify human dna sequences that encoded proteins capable of binding the dre regulatory element. This procedure yielded a single dna clone that encoded a protein containing 284 amino acids. This protein was named dream for the reasons given above. A systematic scan of human tissue material showed that dream was found in the brain, the thymus and thyroid glands, and the testis. dream can bind the dre sequence with enough strength to retard the movement of the sequence on a gel. The binding strength was consistent; one, two or four molecules of dream were bound to a single dre element.

An analysis of the dream protein showed that it contained four regions, or 'domains', that were able to bind calcium. The domains, recognisable from their similarity to calcium-binding domains in other proteins, are known as ' ef hands'. Besides this similarity, dream resembles other calcium-binding proteins: it contains sites that can be modified by the attachment of a phosphate group, a known means of changing the functioning ability of proteins.

However, a direct test of the ability of calcium to bind was still needed. This came about by a demonstration of the fluorescence output of the protein, which was specifically changed by the addition of calcium. When the dream sequence was artificially mutated so as to remove from one to three ef hands from the protein, calcium failed to affect the fluorescence, proving that not only did calcium bind but that it did so through the ef hands. The logical sequence was studied in the crucial experiment.

In this examination, the simultaneous expression of the dream protein repressed the expression of the original human gene. But this it did only when the gene contained a complete dre sequence, and only if no calcium was present. When cellular calcium was made to increase by providing an external signal -- caffeine -- the repression caused by dream was blocked.

Many proteins that bind calcium are known, but this is the first time that anyone has provided direct evidence of the existence of a sensor protein inside the cell nucleus. Upon binding calcium, the nucleus loses its affinity to dna , and so permits a previously repressed gene to start expressing itself.

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