Evidence map›Paper›PMID 25127216›Full record

ArticleCurrent biology : CB2014

Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin.

Amnon Buxboim, Joe Swift, Jerome Irianto, Kyle R Spinler, P C Dave P Dingal, Avathamsa Athirasala, Yun-Ruei C Kao, Sangkyun Cho, Takamasa Harada, Jae-Won Shin and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers.

0numbers the graph read from it
0cells of the map it votes in
235citing papers in PubMed
10.8field-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

235 citing papers in PubMed, 376 citations in OpenAlex.

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175 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

11 authors at 1 institution in 1 country.

Amnon BuxboimMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA; Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joe SwiftMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jerome IriantoMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kyle R SpinlerMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
P C Dave P DingalMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Avathamsa AthirasalaMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yun-Ruei C KaoMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sangkyun ChoMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Takamasa HaradaMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jae-Won ShinMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dennis E DischerMolecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA 19104, USA; Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: discher@seas.upenn.edu.
University of Pennsylvania · US

Funding

Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
YEAST MEMBRANE CYTOSKELETONP01DK032094 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI NARLA, MOHANDAS · 1987 to 2021
$26.7M
Research BaseP30DK090969 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI CARROLL, MARTIN · 2010 to 2015
$5.7M
SPECTRIN EXTENSIBILITY and CD47 CONNECTIONS &FUNCTIONR01HL062352 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 1999 to 2012
$3.3M
Carrier Shape Matters: Filomicelles, Long-circulation, and the EPR effectR01EB007049 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2006 to 2014
$2.8M
Understanding HIV escape using atomic force microscopyR21AI087516 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI DISCHER, DENNIS E., FINKEL, TERRI H · 2010 to 2011
$474k
Myocytes sense substrate stiffness - New materialsR21EB004489 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2005 to 2006
$415k
AFM(T) + FLUORESCENCE MEASUREMENTS ON SINGLE MOLECULESS10RR022575 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2007 to 2007
$382k
Matrix-induced Myogenesis & Pharmaco-Screens of MSCsR21AR056128 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2008 to 2009
$364k
CD47-Display on NanomaterialsR21EB003164 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2003 to 2004
$360k
Worm-like Micelles for Targeted Delivery and ImagingR21EB004000 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2004 to 2005
$348k
NCATS NIH HHS 8UL1TR000003NCATS NIH HHS UL1 TR000003NCRR NIH HHS S10 RR022575NHLBI NIH HHS R01 HL062352NHLBI NIH HHS R01HL062352NIAID NIH HHS R21 AI087516NIAMS NIH HHS R21 AR056128NIBIB NIH HHS R01 EB007049NIBIB NIH HHS R01EB007049NIBIB NIH HHS R21 EB003164NIBIB NIH HHS R21 EB004000NIBIB NIH HHS R21 EB004489NIDDK NIH HHS P01 DK032094NIDDK NIH HHS P01DK032094NIDDK NIH HHS P30DK090969
6 · The paper itself

Abstract

Tissue microenvironments are characterized not only in terms of chemical composition but also by collective properties such as stiffness, which influences the contractility of a cell, its adherent morphology, and even differentiation. The nucleoskeletal protein lamin-A,C increases with matrix stiffness, confers nuclear mechanical properties, and influences differentiation of mesenchymal stem cells (MSCs), whereas B-type lamins remain relatively constant. Here we show in single-cell analyses that matrix stiffness couples to myosin-II activity to promote lamin-A,C dephosphorylation at Ser22, which regulates turnover, lamina physical properties, and actomyosin expression. Lamin-A,C phosphorylation is low in interphase versus dividing cells, and its levels rise with states of nuclear rounding in which myosin-II generates little to no tension. Phosphorylated lamin-A,C localizes to nucleoplasm, and phosphorylation is enriched on lamin-A,C fragments and is suppressed by a cyclin-dependent kinase (CDK) inhibitor. Lamin-A,C knockdown in primary MSCs suppresses transcripts predominantly among actomyosin genes, especially in the serum response factor (SRF) pathway. Levels of myosin-IIA thus parallel levels of lamin-A,C, with phosphosite mutants revealing a key role for phosphoregulation. In modeling the system as a parsimonious gene circuit, we show that tension-dependent stabilization of lamin-A,C and myosin-IIA can suitably couple nuclear and cell morphology downstream of matrix mechanics.

Indexed as

Cell DifferentiationElasticityExtracellular MatrixFeedback, PhysiologicalHumansLamin Type AMesenchymal Stem CellsNonmuscle Myosin Type IIAPhosphorylationSingle-Cell AnalysisLamin Type ANonmuscle Myosin Type IIA

Identifiers

PMID25127216
PMCPMC4373646
OpenAlexW2057025275

What OpenQuestion holds

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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.