Evidence map›Paper›PMID 24695858›Full record

ArticleJournal of cell science2014

Regulation of Rac1 translocation and activation by membrane domains and their boundaries.

Konstadinos Moissoglu, Volker Kiessling, Chen Wan, Brenton D Hoffman, Andres Norambuena, Lukas K Tamm, Martin Alexander Schwartz

Abstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
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  9. Roles of Membrane Domains in Integrin-Mediated Cell Adhesion.International journal of molecular sciences · 2020
    Review
  10. Lung Endothelial Transcytosis.Comprehensive Physiology · 2020
    Review
  11. Palmitoylated Proteins in Dendritic Spine Remodeling.Frontiers in synaptic neuroscience · 2020
    Article
  12. Article
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  15. Review
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  20. mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017
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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

7 authors at 1 institution in 1 country.

Konstadinos MoissogluRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA konstadinos.moissoglu@nih.gov martin.schwartz@yale.edu.
Volker KiesslingCenter for Membrane Biology, University of Virginia, Charlottesville, VA 22908, USA Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
Chen WanCenter for Membrane Biology, University of Virginia, Charlottesville, VA 22908, USA Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
Brenton D HoffmanRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Andres NorambuenaRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Lukas K TammCenter for Membrane Biology, University of Virginia, Charlottesville, VA 22908, USA Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
Martin Alexander SchwartzRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA konstadinos.moissoglu@nih.gov martin.schwartz@yale.edu.
University of Virginia · US

Funding

STRUCTUREU54GM064346 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI IMPERIALI, BARBARA · 2001 to 2010
$74.9M
Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Thomas P. Loughran · 1987 to 2026
$72.1M
Structural Dynamics of the Exocytotic Fusion Machine in Neurons.P01GM072694 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 2005 to 2021
$17.4M
Structure, Assembly, and Function of Outer Membrane ProteinsR01GM051329 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 1997 to 2018
$6.4M
The Rho Family GTPases in Integrin SignalingR01GM047214 · NIGMS · YALE UNIVERSITY · PI SCHWARTZ, MARTIN A · 1991 to 2020
$6.3M
VIRAL SPIKE GLYCOPROTEIN-MEDIATED MEMBRANE POTENTIALR01AI030557 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 1991 to 2022
$6.2M
Integrins in the Endothelial Response to Fluid Shear StressR01HL075092 · NHLBI · YALE UNIVERSITY · PI SCHWARTZ, MARTIN A · 2004 to 2019
$5.1M
VACCINE DELIVERY SYSTEM FOR LIVE ROTAVIRUS VACCINESR43AI030577 · NIAID · SECRETECH, INC. · PI MATSUOKA, YUMIKO · 1990 to 1990
–
VACCINE DELIVERY SYSTEM FOR LIVE ROTAVIRUS VACCINESR44AI030577 · NIAID · SECRETECH, INC. · PI NOVAK, MIROSLAV · 1992 to 1992
–
NCI NIH HHS P30 CA044579NHLBI NIH HHS R01 HL075092NIAID NIH HHS R01 AI030557NIAID NIH HHS R37 AI30577NIGMS NIH HHS P01 GM072694NIGMS NIH HHS P01 GM51329NIGMS NIH HHS R01 GM047214NIGMS NIH HHS R01 GM051329NIGMS NIH HHS R01 GM47214NIGMS NIH HHS U54 GM064346NIGMS NIH HHS U54 GM64346
6 · The paper itself

Abstract

The activation of Rac1 and related Rho GTPases involves dissociation from Rho GDP-dissociation inhibitor proteins and translocation to membranes, where they bind effectors. Previous studies have suggested that the binding of Rac1 to membranes requires, and colocalizes with, cholesterol-rich liquid-ordered (lo) membrane domains (lipid rafts). Here, we have developed a fluorescence resonance energy transfer (FRET) assay that robustly detects Rac1 membrane targeting in living cells. Surprisingly, FRET with acceptor constructs that were targeted to either raft or non-raft areas indicated that Rac1 was present in both regions. Functional studies showed that Rac1 localization to non-raft regions decreased GTP loading as a result of inactivation by GTPase-activating proteins. In vitro, Rac1 translocation to supported lipid bilayers also required lo domains, yet Rac1 was concentrated in the liquid-disordered (ld) phase. Single-molecule analysis demonstrated that translocation occurred preferentially at lo-ld boundaries. These results, therefore, suggest that Rac1 translocates to the membrane at domain boundaries, then diffuses into raft and non-raft domains, which controls interactions. These findings resolve discrepancies in our understanding of Rac biology and identify novel mechanisms by which lipid rafts modulate Rho GTPase signaling.

Indexed as

AnimalsCell MembraneFluorescence Resonance Energy TransferGTPase-Activating ProteinsHEK293 CellsHumansMembrane MicrodomainsMiceNIH 3T3 CellsProtein BindingProtein Transportrac1 GTP-Binding Proteinrho-Specific Guanine Nucleotide Dissociation InhibitorsSignal TransductionUnilamellar LiposomesGTPase-Activating Proteinsrac1 GTP-Binding Proteinrho-Specific Guanine Nucleotide Dissociation InhibitorsUnilamellar LiposomesDomain boundariesFRETLipid raftsRacSupported bilayers

Identifiers

PMID24695858
PMCPMC4038948
OpenAlexW2025713414

What OpenQuestion holds

Textmetadata
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.