Evidence map›Paper›PMID 22458296›Full record

ArticleJournal of thrombosis and haemostasis : JTH2012

Targeted gene inactivation reveals a functional role of calpain-1 in platelet spreading.

S M Kuchay, A J Wieschhaus, M Marinkovic, I M Herman, A H Chishti

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Trial
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  10. Activity-dependent rapid local RhoA synthesis is required for hippocampal synaptic plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    Article
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  14. Rho GTPases in platelet function.Journal of thrombosis and haemostasis : JTH · 2013
    Review
  15. Article
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

5 authors at 2 institutions in 1 country.

S M KuchayDepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL, USA.
A J Wieschhaus
M Marinkovic
I M Herman
A H Chishti
Tufts University · USHoward Hughes Medical Institute · US

Funding

Cytoskeletal Regulation of Erythrocyte Glucose Transporter-1R01HL095050 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 2009 to 2012
$1.6M
Calpain-1 Signaling Pathways in PlateletsR01HL089517 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHISHTI, ATHAR H. · 2009 to 2012
$1.6M
Howard Hughes Medical InstituteNHLBI NIH HHS HL089517NHLBI NIH HHS HL095050NHLBI NIH HHS R01 HL089517NHLBI NIH HHS R01 HL095050
6 · The paper itself

Abstract

backgroundCalpains are implicated in a wide range of cellular functions including the maintenance of hemostasis via the regulation of cytoskeletal modifications in platelets.

objectivesDetermine the functional role of calpain isoforms in platelet spreading. METHODS AND

resultsPlatelets from calpain-1(-/-) mice show enhanced spreading on collagen- and fibrinogen-coated surfaces as revealed by immunofluorescence, differential interference contrast (DIC) and scanning electron microscopy. The treatment of mouse platelets with MDL, a cell permeable inhibitor of calpains 1/2, resulted in increased spreading. The PTP1B-mediated enhanced tyrosine dephosphorylation in calpain-1(-/-) platelets did not fully account for the enhanced spreading as platelets from the double knockout mice lacking calpain-1 and PTP1B showed only a partial rescue of the spreading phenotype. In non-adherent platelets, proteolysis and GTPase activity of RhoA and Rac1 were indistinguishable between the wild-type (WT) and calpain-1(-/-) platelets. In contrast, the ECM-adherent calpain-1(-/-) platelets showed higher Rac1 activity at the beginning of spreading, whereas RhoA was more active at later time points. The ECM-adherent calpain-1(-/-) platelets showed an elevated level of RhoA protein but not Rac1 and Cdc42. Proteolysis of recombinant RhoA, but not Rac1 and Cdc42, indicates that RhoA is a calpain-1 substrate in vitro.

conclusionsPotentiation of the platelet spreading phenotype in calpain-1(-/-) mice suggests a novel role of calpain-1 in hemostasis, and may explain the normal bleeding time observed in the calpain-1(-/-) mice.

Indexed as

Cell ShapeGene SilencingAnimalsBlood PlateletsCalpaincdc42 GTP-Binding ProteinCell AdhesionCollagenEnzyme ActivationFibrinogenGenotypeHemostasisHumansMiceMice, KnockoutMicroscopy, Electron, ScanningCalpainCapn1 protein, mousecdc42 GTP-Binding ProteinCollagenFibrinogenProtease InhibitorsProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 1Ptpn1 protein, mouserac1 GTP-Binding ProteinRAC1 protein, humanRecombinant ProteinsrhoA GTP-Binding ProteinRhoA protein, mouserho-Associated Kinasesrho GTP-Binding ProteinsTyrosine

Identifiers

PMID22458296
PMCPMC3956748
OpenAlexW1586375807

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Registered trials

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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.