ArticleProceedings of the National Academy of Sciences of the United States of America2011
Mechanistic basis of bell-shaped dependence of inositol 1,4,5-trisphosphate receptor gating on cytosolic calcium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 30 citations in OpenAlex.
- Ligand sensitivity of type-1 inositol 1,4,5-trisphosphate receptor is enhanced by the D2594K mutation.Pflugers Archiv : European journal of physiology · 2023Article
- Endocannabinoid signaling in astrocytes.Glia · 2023Review
- Extracellular histones induce calcium signals in the endothelium of resistance-sized mesenteric arteries and cause loss of endothelium-dependent dilation.American journal of physiology. Heart and circulatory physiology · 2019Article
- Dual-FRET imaging of IPScientific reports · 2019Article
- Structural basis for the regulation of inositol trisphosphate receptors by CaNature structural & molecular biology · 2018Article
- Coupling all-atom molecular dynamics simulations of ions in water with Brownian dynamics.Proceedings. Mathematical, physical, and engineering sciences · 2016Article
- Regulatory Mechanisms of Endoplasmic Reticulum Resident IP3 Receptors.Journal of molecular neuroscience : MN · 2015Review
- Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Single-molecule tracking of inositol trisphosphate receptors reveals different motilities and distributions.Biophysical journal · 2014Article
- N-terminus oligomerization is conserved in intracellular calcium release channels.The Biochemical journal · 2014Article
- Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts.Biophysics (Nagoya-shi, Japan) · 2014Article
- Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity.Frontiers in computational neuroscience · 2012Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) is an intracellular Ca(2+) release channel, and its opening is controlled by IP(3) and Ca(2+). A single IP(3) binding site and multiple Ca(2+) binding sites exist on single subunits, but the precise nature of the interplay between these two ligands in regulating biphasic dependence of channel activity on cytosolic Ca(2+) is unknown. In this study, we visualized conformational changes in IP(3)R evoked by various concentrations of ligands by using the FRET between two fluorescent proteins fused to the N terminus of individual subunits. IP(3) and Ca(2+) have opposite effects on the FRET signal change, but the combined effect of these ligands is not a simple summative response. The bell-shaped Ca(2+) dependence of FRET efficiency was observed after the subtraction of the component corresponding to the FRET change evoked by Ca(2+) alone from the FRET changes evoked by both ligands together. A mutant IP(3)R containing a single amino acid substitution at K508, which is critical for IP(3) binding, did not exhibit this bell-shaped Ca(2+) dependence of the subtracted FRET efficiency. Mutation at E2100, which is known as a Ca(2+) sensor, resulted in ∼10-fold reduction in the Ca(2+) dependence of the subtracted signal. These results suggest that the subtracted FRET signal reflects IP(3)R activity. We propose a five-state model, which implements a dual-ligand competition response without complex allosteric regulation of Ca(2+) binding affinity, as the mechanism underlying the IP(3)-dependent regulation of the bell-shaped relationship between the IP(3)R activity and cytosolic Ca(2+).
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