Nuclear pore disassembly from endoplasmic reticulum membranes promotes Ca2+ 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.
Boulware
Michael J
MJ
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
Marchant
Jonathan S
JS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure; D022022:Nuclear Pore / Q000502:physiology* / Q000648:ultrastructure; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D014982:Xenopus laevis
D002118:Calcium