Just better bones? No, calcium plays other, more crucial roles within our bodies
every schoolchild knows that calcium is very important for growth, particu-larly so as it helps our bodies develop better bones and teeth. Well, it turns out that calcium has 'other' important roles to play too. It is a crucial element in the intricate processes of inter-cellular communication, known as signal transduction, as also between the external world and our sense organs. The intricacy of signal transduction, especially of the part played by calcium, is brought out in an elegant piece of work reported by Sangeeta Chawla and her colleagues from the Laboratory of Molecular Biology in Cambridge, uk, ( Science , Vol 281, No 2587).
Like the pituitary cells, most other cells start dividing when presented with agents known as mitogens. Cell division requires the synthesis of a number of specialised proteins, and that, in turn, depends on 'turning on' the activities of genes that encode those proteins. In short, the mitogen has to 'activate' certain genes, to transcribe. In order to do so, the cell has to first cause its internal calcium levels to increase. The calcium stimulates or rather, activates, the right genes. Cells normally increase their calcium levels in two ways: first, by pulling calcium in from the outside and secondly, by releasing calcium from stores inside themselves. This increase in calcium stimulates a cascade, part of which involves recruitment of a protein known as cbp which, in combination with another protein known as creb , stimulates gene expression.
Chawla and her team have made the interesting discovery that even though both depend on a rise in internal calcium, changes induced by these two proteins can be differentiated. This is done by separating the calcium signal into two distinct spatial components. One consists of an increase in calcium within the body of the cell, the cytoplasm. The other is a calcium increase caused within the nucleus, which contains the genetic material. It turns out that an increase in cytoplasmic calcium provides the cbp recruitment signal but is unable to stimulate the transcription step which is mediated jointly by cbp and creb . The latter requires an increase in the calcium level within the nucleus as well as an accessory small molecule known as cyclic amp (c amp ). Nuclear calcium activates an enzyme that, together with c amp , influences a specific portion of the cbp molecule that is important for gene transcription.
There are three take-home lessons of this study. Firstly, small molecules can be present at different concentrations at different locations within the same tiny cell that are a thirtieth of a millimetre or smaller in diameter. Secondly, regional differences can be of crucial importance within the living cell. And finally, the same signal coming from the outside is differently analysed in the nucleus and the cytoplasm, and a signal in the cytoplasm does not automatically mean one in the nucleus. There. We go home enlightened.
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