Nuclear pore disassembly from endoplasmic reticulum membranes promotes Ca 2+ signalling competency

The functionality of the endoplasmic reticulum (ER) as a Ca 2+ storage organelle is supported by families of Ca 2+ pumps, buffers and channels that regulate Ca 2+ fluxes between the ER lumen and cytosol. Although many studies have identified heterogeneities in Ca 2+ fluxes throughout the ER, the question of how differential functionality of Ca 2+ channels is regulated within proximal regions of the same organelle is unresolved. Here, we studied the in vivo dynamics of an ER subdomain known as annulate lamellae (AL), a cytoplasmic nucleoporin‐containing organelle widely used in vitro to study the mechanics of nuclear envelope breakdown. We show that nuclear pore complexes (NPCs) within AL suppress local Ca 2+ signalling activity, an inhibitory influence relieved by heterogeneous dissociation of nucleoporins to yield NPC‐denuded ER domains competent at Ca 2+ signalling. Consequently, we propose a novel generalized role for AL – reversible attenuation of resident protein activity – such that regulated AL (dis)assembly via a kinase/phosphatase cycle allows cells to support rapid gain/loss‐of‐function transitions in cellular physiology.