Spatial organization of intracellular Ca2+ signals

AbstractThe ability of Ca2+, the simplest of all intracellular messengers, selectively to regulate so many cellular behaviours is due largely to the complex spatiotemporal organization of intracellular Ca2+ signals. Most signalling pathways, including those that culminate in Ca2+ signals, comprise sequences of protein–protein interactions linked by diffusible messengers. Using specific examples to illustrate key principles, we consider the roles of both components in defining the spatial organization of Ca2+ signals. We discuss evidence that regulation of most Ca2+ channels by Ca2+ contributes to controlling the duration of Ca2+ signals, to signal integration and, via Ca2+-induced Ca2+ release, to defining the spatial spread of Ca2+ signals. We distinguish two types of protein–protein interaction: scaffolds that allow rapid local transfer of diffusible messengers between signalling proteins, and interactions that directly transfer information between signalling proteins. Store-operated Ca2+ entry provides a ubiquitous example of the latter, and it serves also to illustrate how Ca2+ signals can be organized at different levels of spatial organization – from interactions between proteins to interactions between organelles