In This Issue

Ca²⁺ is one of the most versatile signalling factors identified to date. So we've dedicated this issue to Ca²⁺ to give you a flavour of its many different signalling functions — inside and outside the cell, during embryonic development, in the regulation and dysregulation of cardiac contractility and as a modulator of programmed cell death.

Much of the recent progress in studying intracellular Ca²⁺ signalling and dynamics was made possible by the development of synthetic and protein-based Ca²⁺ sensors, which can be used to image Ca²⁺ inside the cell. Tullio Pozzan and colleagues provide an overview of how Ca²⁺ sensors developed on page 579, and discuss how they might be further optimized in the future.

On page 517, Michael J. Berridge and colleagues propose that many of the Ca²⁺-signalling components — collectively known as the Ca²⁺-signalling toolkit — are regulated by Ca²⁺ itself, and that alterations in this homeostatic remodelling mechanism might cause severe diseases.

On the subject of disease, phospholamban is a small inhibitor that regulates the SERCA2a Ca²⁺ pump and, as a result, cardiac contractility. Mutations in the phospholamban gene can cause dilated cardiomyopathy and, on page 566, David H. MacLennan and Evangelia G. Kranias discuss structural and functional studies that might eventually lead to new therapies.

Although the intracellular signalling functions of Ca²⁺ have been studied extensively, its role outside the cell is less well understood. The identification of an extracellular Ca²⁺-sensing receptor has, however, indicated that Ca²⁺ might signal outside the cell and, on page 530, Aldebaran M. Hofer and Edward M. Brown discuss evidence that this is indeed the case.

And finally, this month we would like to bid a fond farewell to Alison Mitchell — the journal's inspirational launch Editor.