ABSTRACT
This chapter provides an overview of non-Orai–stromal interaction molecule (STIM) interaction partners, covering store-operated calcium entry (SOCE) modulators, alternative effectors, and scaffolds with an outline of the experimental evidence and details of their physical integration into STIM signal complexes, as well as a discussion of the (patho)physiological significance of these interactions. The signaling function of STIM embraces not only endoplasmic reticulum (ER) luminal Ca2+ sensing and the regulation of Ca2+ handling proteins but also dynamic architectural ER remodeling. Lipid recognition and ER–PM bridging via the STIM K-domain represents a potential mechanism of nanojunctional scaffolding. Structural motifs that confer the principal functions of STIM1 and STIM2 in SOCE have been clearly delineated, and, more recently, high-resolution structural information has been obtained for parts of STIM–Orai coupling domains. Communication between Orai and transient receptor potential canonical channels is expected to occur due to overlapping interactions with STIM and by Ca2+-mediated cross talk in junctional nanodomains.
