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Dr Pulak Kar, Professor Anant Parekh and colleagues are a step closer to understanding how specificity is achieved in the immune system.

Of the thousands of chemical signals that land on a cell’s surface each day, only a handful of intracellular messengers are used to produce a physiological effect. Amongst the small number of signals employed, intracellular calcium is the most widespread, activating a range of important responses including neurotransmission, beating of the heart, energy production and cell growth. However, with the same message capable of activating so many different processes comes the question of specificity: how does a cell know what to do when the intracellular calcium levels rise? Dr Pulak Kar, Professor Anant Parekh and colleagues are a step closer to understanding how specificity is achieved in the immune system. The team’s research in Current Biology (24, 1361-1368) show that a protein signalling complex forms at the cell periphery close to a calcium channel called the CRAC channel that lets calcium ions enter the cell. As the calcium enters, its target is immediately and selectively activated. This mechanism explains how different ways of increasing calcium activates different cellular responses. The results also reveal that targeting the CRAC channel therapeutically should be an effective approach to control the severity of an immune response.