Evidence map›Paper›PMID 25964668›Full record

ArticleBlood2015

Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis.

Zhenhua Sui, Roberta B Nowak, Chad Sanada, Stephanie Halene, Diane S Krause, Velia M Fowler

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 35 citations in OpenAlex.

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  8. Flow-accelerated platelet biogenesis is due to an elasto-hydrodynamic instability.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  12. New insights into cytoskeletal remodeling during platelet production.Journal of thrombosis and haemostasis : JTH · 2019
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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

6 authors at 3 institutions in 1 country.

Zhenhua SuiDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA;
Roberta B NowakDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA;
Chad SanadaDepartment of Laboratory Medicine, Yale Stem Cell Center, and.
Stephanie HaleneDivision of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Diane S KrauseDepartment of Laboratory Medicine, Yale Stem Cell Center, and.
Velia M FowlerDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA;
Scripps Research Institute · USYale Cancer Center · USYale University · US

Funding

Yale Cooperative Hematology Specialized Core CenterU54DK106857 · NIDDK · YALE UNIVERSITY · PI JOHN HWA, Diane S Krause · 2015 to 2026
$9.7M
IMMUNOHEMATOLOGY/TRANSFUSION MEDICINE RESEARCH TRAININGT32HL007974 · NHLBI · YALE UNIVERSITY · PI JEANNE E HENDRICKSON, Diane S Krause · 2001 to 2026
$8.1M
Capping Actin Growth in Erythroid and Nonerythroid CellsR01HL083464 · NHLBI · UNIVERSITY OF DELAWARE · PI FOWLER, VELIA M · 2006 to 2019
$7.1M
Mechanisms of megakaryocyte maturationR01DK094934 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2012 to 2016
$2.7M
MKL in megakaryocytopoiesisR01DK086267 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2010 to 2013
$1.5M
NHLBI NIH HHS R01 HL083464NHLBI NIH HHS R01-HL083464NHLBI NIH HHS T32 HL007974NIDDK NIH HHS DK094934NIDDK NIH HHS R01 DK086267NIDDK NIH HHS R01 DK094934NIDDK NIH HHS U54 DK106857
6 · The paper itself

Abstract

The actin cytoskeleton is important for platelet biogenesis. Tropomodulin-3 (Tmod3), the only Tmod isoform detected in platelets and megakaryocytes (MKs), caps actin filament (F-actin) pointed ends and binds tropomyosins (TMs), regulating actin polymerization and stability. To determine the function of Tmod3 in platelet biogenesis, we studied Tmod3(-/-) embryos, which are embryonic lethal by E18.5. Tmod3(-/-) embryos often show hemorrhaging at E14.5 with fewer and larger platelets, indicating impaired platelet biogenesis. MK numbers are moderately increased in Tmod3(-/-) fetal livers, with only a slight increase in the 8N population, suggesting that MK differentiation is not significantly affected. However, Tmod3(-/-) MKs fail to develop a normal demarcation membrane system (DMS), and cytoplasmic organelle distribution is abnormal. Moreover, cultured Tmod3(-/-) MKs exhibit impaired proplatelet formation with a wide range of proplatelet bud sizes, including abnormally large proplatelet buds containing incorrect numbers of von Willebrand factor-positive granules. Tmod3(-/-) MKs exhibit F-actin disturbances, and Tmod3(-/-) MKs spreading on collagen fail to polymerize F-actin into actomyosin contractile bundles. Tmod3 associates with TM4 and the F-actin cytoskeleton in wild-type MKs, and confocal microscopy reveals that Tmod3, TM4, and F-actin partially colocalize near the membrane of proplatelet buds. In contrast, the abnormally large proplatelets from Tmod3(-/-) MKs show increased F-actin and redistribution of F-actin and TM4 from the cortex to the cytoplasm, but normal microtubule coil organization. We conclude that F-actin capping by Tmod3 regulates F-actin organization in mouse fetal liver-derived MKs, thereby controlling MK cytoplasmic morphogenesis, including DMS formation and organelle distribution, as well as proplatelet formation and sizing.

Indexed as

Actin CytoskeletonAnimalsApoptosisBlood PlateletsBlotting, WesternCell MembraneCell ProliferationCells, CulturedCytoplasmEmbryo, MammalianFemaleFluorescent Antibody TechniqueHematopoiesisHemorrhageImmunoprecipitationMegakaryocytesTmod3 protein, mouseTropomodulin

Identifiers

PMID25964668
PMCPMC4513252
OpenAlexW1522349278

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.