STIM proteins: Integrators of signalling pathways in development, differentiation and disease

Abstract

The stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum Ca2+ sensors, serving to detect changes in receptor-mediated ER Ca2+ store depletion and to relay this information to plasma membrane localized proteins, including the store-operated Ca2+ channels of the ORAI family. The resulting Ca2+ influx sustains the high cytosolic Ca2+ levels required for activation of many intracellular signal transducers such as the NFAT family of transcription factors. Models of STIM protein deficiency in mice, Drosophila melanogaster and Caenorhabditis elegans, in addition to the phenotype of patients bearing mutations in STIM1 have provided great insight into the role of these proteins in cell physiology and pathology. It is now becoming clear that STIM1 and STIM2 are critical for the development and functioning of many cell types, including lymphocytes, skeletal and smooth muscle myoblasts, adipocytes and neurons, and can interact with a variety of signalling proteins and pathways in a cell- and tissue-type specific manner. This review focuses on the role of STIM proteins in development, differentiation and disease, in particular highlighting the functional differences between STIM1 and STIM2. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.