Arriving at the next level of complexity in IP3R and SOCE signaling

The endoplasmic reticulum (ER) has long been recognized as the master regulator of cellular Ca2+ signaling. In this context, IP3R channels may be envisioned as this conductor's baton, which enables virtuous orchestration of cellular Ca(2+ )signaling tunes. IP(3)Rs serve the generation of spatiotemporally defined Ca2+ changes and are key for the ER ' s function as an autonomous Ca2+ signaling unit, which is able to govern its own refilling from the extracellular Ca2+ pool. As yet, IP3R signaling has been primarily attributed to its precisely-tunable Ca2+ channel function and IP3-mediated control over Ca2+ levels within signaling domains. A recent report from the Hasan laboratory [1] provides evidence for an as yet overlooked function of IP(3)R1 in terms of supporting STIM/Oraimediated SOCE in neurons. IP(3)R1 is demonstrated to remarkably facilitate productive STIM-Orai interactions and SOCE by a process that is triggered by IP3 but independent of the receptors' function as an ER Ca2+ channel.

Automated summary

The endoplasmic reticulum (ER) is crucial for cellular calcium signaling, with IP3R channels playing a key role in regulating calcium levels. Recent research has uncovered a previously overlooked function of IP3R1 in neurons, showing its involvement in supporting STIM/Orai-mediated store-operated calcium entry (SOCE).