Evidence map›Paper›PMID 25057023›Full record

ArticleMolecular biology of the cell2014

Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at endoplasmic reticulum-plasma membrane junctions.

Minnie M Wu, Elizabeth D Covington, Richard S Lewis

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
6.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 116 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Minnie M WuDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Elizabeth D CovingtonDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Richard S LewisDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Stanford University · US

Funding

MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Ion Channels and Signaling Mechanisms in T LymphocytesR37GM045374 · NIGMS · STANFORD UNIVERSITY · PI LEWIS, RICHARD S · 2012 to 2021
$6.2M
NIAID NIH HHS T32 AI007290NIGMS NIH HHS R37 GM045374NIGMS NIH HHS R37GM45374
6 · The paper itself

Abstract

Following endoplasmic reticulum (ER) Ca(2+) depletion, STIM1 and Orai1 complexes assemble autonomously at ER-plasma membrane (PM) junctions to trigger store-operated Ca(2+) influx. One hypothesis to explain this process is a diffusion trap in which activated STIM1 diffusing in the ER becomes trapped at junctions through interactions with the PM, and STIM1 then traps Orai1 in the PM through binding of its calcium release-activated calcium activation domain. We tested this model by analyzing STIM1 and Orai1 diffusion using single-particle tracking, photoactivation of protein ensembles, and Monte Carlo simulations. In resting cells, STIM1 diffusion is Brownian, while Orai1 is slightly subdiffusive. After store depletion, both proteins slow to the same speeds, consistent with complex formation, and are confined to a corral similar in size to ER-PM junctions. While the escape probability at high STIM:Orai expression ratios is <1%, it is significantly increased by reducing the affinity of STIM1 for Orai1 or by expressing the two proteins at comparable levels. Our results provide direct evidence that STIM-Orai complexes are trapped by their physical connections across the junctional gap, but also reveal that the complexes are surprisingly dynamic, suggesting that readily reversible binding reactions generate free STIM1 and Orai1, which engage in constant diffusional exchange with extrajunctional pools.

Indexed as

CalciumCalcium ChannelsCell MembraneDiffusionEndoplasmic ReticulumFluorescence Resonance Energy TransferGene Expression RegulationHEK293 CellsHumansIon TransportMembrane ProteinsMolecular Dynamics SimulationMonte Carlo MethodMutationNeoplasm ProteinsORAI1 ProteinCalciumCalcium ChannelsMembrane ProteinsNeoplasm ProteinsORAI1 ProteinORAI1 protein, humanSTIM1 protein, humanStromal Interaction Molecule 1

Identifiers

PMID25057023
PMCPMC4230625
OpenAlexW2069637152

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.