Calcium regulation of nucleocytoplasmic transport

Abstract

Bidirectional trafficking of macromolecules between the cytoplasm and the nucleus is mediated by the nuclear pore complexes (NPCs) embedded in the nuclear envelope (NE) of eukaryotic cell. The NPC functions as the sole pathway to allow for the passive diffusion of small molecules and the facilitated translocation of larger molecules. Evidence shows that these two transport modes and the conformation of NPC can be regulated by calcium stored in the lumen of nuclear envelope and endoplasmic reticulum. However, the mechanism of calcium regulation remains poorly understood. In this review, we integrate data on the observations of calciumregulated structure and function of the NPC over the past years. Furthermore, we highlight challenges in the measurements of dynamic conformational changes and transient transport kinetics in the NPC. Finally, an innovative imaging approach, single-molecule superresolution fluorescence microscopy, is introduced and expected to provide more insights into the mechanism of calcium-regulated nucleocytoplasmic transport.

Role of the nuclear envelope in calcium signalling

“…A recent study in liver cells, using localised two-photon activation of photoactivatable GFP, demonstrates that hormones that increase cytosolic Ca 2+ concentration increased the permeability of the nuclear membrane (O'Brien, et al, 2007). These studies and others illustrate the discrepancies on the role of Ca 2+ on the permeability of the NPC, they also indicate that both luminal and cytoplasmic Ca 2+ may have an important role in regulating trafficking of macromolecules between the cytoplasm and the nucleoplasm (for review and discussion see Bootman, et al, 2009, Sarma andYang, 2011). This may provide a mechanism to mediate the entry of transcription factors or other regulatory molecules and to regulate gene transcription in target cells.…”

New Calcium‐Selective Smart Contrast Agents for Magnetic Resonance Imaging

“…Four different agents were designed and synthesized, Gd-DOPTRA- (2)(3)(4)(5), which share structural similarity to our previously published molecule, Gd-DOPTRA-1 ( Figure 1). [7b] We sought for higher Ca 2 + -dependent relaxivity changes and improved selectivity of the agents toward Ca 2 + in complex biological media with stability toward release of acetate arm (the Supporting Information, Figure S1).…”

“…The development of fluorescent dyes has greatly helped to our understanding of this critical role played by Ca 2 + . [5] However the current limitation of the depth of penetration of optical imaging techniques and the production of side products resulting from the photobleaching of the dyes when exposed to light narrows the applications of this modality to only superficial regions.…”

Regulation of nuclear envelope permeability in cell death and survival

“…To account for the asynchronicity of the apoptotic process, data from each time series were split into two parts and displayed Numerous studies have proposed a role for Ca 2+ in the regulation of NPC structure and function. The underlying mechanisms are not fully clear yet (reviewed in [20][21][22] ). The NE harbours functional inositol(1,4,5)-trisphosphate receptors (InsP3Rs), as well as ryanodine receptors (RyRs) and nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs).…”