Evidence map›Paper›PMID 27280401›Full record

ArticlePLoS biology2016

Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration.

Alba Diz-Muñoz, Kevin Thurley, Sana Chintamen, Steven J Altschuler, Lani F Wu, Daniel A Fletcher, Orion D Weiner

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed
14.8field-weighted citation impact, top 1% 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

121 citing papers in PubMed, 215 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Chemical and Mechanical Regulation of Leukocyte Migration.Cold Spring Harbor perspectives in biology · 2026
    Review
  8. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
    Review
  9. Article
  10. Article
  11. Signaling and actin waves at a glance.Journal of cell science · 2025
    Review
  12. Article
  13. mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. The Role of the Swollen State in Cell Proliferation.The Journal of membrane biology · 2025
    Review
  18. Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025
    Review
  19. Cellular mechanisms of traumatic brain injury.npj biological physics and mechanics · 2025
    Review
  20. Article

61 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

7 authors at 2 institutions in 1 country.

Alba Diz-MuñozCardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
Kevin ThurleyDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
Sana ChintamenCardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
Steven J AltschulerDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
Lani F WuDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.ORCID 0000-0002-0052-7537
Daniel A FletcherBioengineering Department and Biophysics Program, University of California Berkeley, Berkeley, California, United States of America.
Orion D WeinerCardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
University of California, San Francisco · USUniversity of California, Berkeley · US

Funding

Cellular Decision Making Diversity SupplementR35GM118167 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Orion D Weiner · 2016 to 2026
$10.3M
Signal Integration in Neutrophil ChemotaxisR01GM084040 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEINER, ORION D · 2008 to 2015
$2.6M
Mechanical Regulation of Actin NetworksR01GM074751 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLETCHER, DANIEL A · 2008 to 2015
$2.4M
(PQD1) An Iterative Approach for Overcoming Evolving Targeted Therapy ResistanceR01CA185404 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WU, LANI F · 2014 to 2017
$1.3M
Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistanceR01GM112690 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALTSCHULER, STEVEN J · 2015 to 2018
$1.3M
A membrane encapsulation system for cellular reconstitutionR01GM114344 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLETCHER, DANIEL A · 2015 to 2018
$1.2M
NCI NIH HHS R01 CA185404NIGMS NIH HHS R01 GM074751NIGMS NIH HHS R01 GM084040NIGMS NIH HHS R01 GM112690NIGMS NIH HHS R01 GM114344NIGMS NIH HHS R35 GM118167
6 · The paper itself

Abstract

For efficient polarity and migration, cells need to regulate the magnitude and spatial distribution of actin assembly. This process is coordinated by reciprocal interactions between the actin cytoskeleton and mechanical forces. Actin polymerization-based protrusion increases tension in the plasma membrane, which in turn acts as a long-range inhibitor of actin assembly. These interactions form a negative feedback circuit that limits the magnitude of membrane tension in neutrophils and prevents expansion of the existing front and the formation of secondary fronts. It has been suggested that the plasma membrane directly inhibits actin assembly by serving as a physical barrier that opposes protrusion. Here we show that efficient control of actin polymerization-based protrusion requires an additional mechanosensory feedback cascade that indirectly links membrane tension with actin assembly. Specifically, elevated membrane tension acts through phospholipase D2 (PLD2) and the mammalian target of rapamycin complex 2 (mTORC2) to limit actin nucleation. In the absence of this pathway, neutrophils exhibit larger leading edges, higher membrane tension, and profoundly defective chemotaxis. Mathematical modeling suggests roles for both the direct (mechanical) and indirect (biochemical via PLD2 and mTORC2) feedback loops in organizing cell polarity and motility-the indirect loop is better suited to enable competition between fronts, whereas the direct loop helps spatially organize actin nucleation for efficient leading edge formation and cell movement. This circuit is essential for polarity, motility, and the control of membrane tension.

Indexed as

Cell MovementActin CytoskeletonActinsBlotting, WesternCell MembraneCell PolarityHEK293 CellsHL-60 CellsHumansMechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMicroscopy, FluorescenceModels, BiologicalMultiprotein ComplexesNeutrophilsPhospholipase DActinsMechanistic Target of Rapamycin Complex 2Multiprotein ComplexesPhospholipase Dphospholipase D2TOR Serine-Threonine Kinases

Identifiers

PMID27280401
PMCPMC4900667
OpenAlexW2414012998

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.