Evidence map›Paper›PMID 25468568›Full record

ArticleBlood2015

Dynamin 2-dependent endocytosis is required for normal megakaryocyte development in mice.

Markus Bender, Silvia Giannini, Renata Grozovsky, Terese Jönsson, Hilary Christensen, Fred G Pluthero, Amy Ko, Ann Mullally, Walter H A Kahr, Karin M Hoffmeister and 1 more

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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  7. In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021
    Review
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  12. C-Cbl regulates c-MPL receptor trafficking and its internalization.Journal of cellular and molecular medicine · 2020
    Article
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  16. Review
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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

11 authors at 4 institutions in 3 countries.

Markus BenderDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Silvia GianniniDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Renata GrozovskyDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Terese JönssonDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
Hilary ChristensenProgram in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; and.
Fred G PlutheroProgram in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; and.
Amy KoDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Ann MullallyDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Walter H A KahrProgram in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; and Department of Pediatrics and Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Karin M HoffmeisterDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Hervé FaletDivision of Hematology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA;
Brigham and Women's Hospital · USHarvard University · USHospital for Sick Children · CAUniversity of Toronto · CA

Funding

WIP in TCR signaling and actin reorganizationP01HL059561 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI SNAPPER, SCOTT B · 1997 to 2012
$21.8M
REGULATION OF LACTOSAMINYL GLYCAN BIOSYNTHESIS IN HEMATOPOIETIC CELLSP01HL107146 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LAU, JOSEPH TY · 2011 to 2017
$17.7M
Carbohydrate-Mediated Platelet ClearanceR01HL089224 · NHLBI · VERSITI WISCONSIN, INC. · PI Karin Maria Hoffmeister · 2007 to 2026
$9.3M
Filamin A - Syk Interactions Modulate Platelet ITAM-based SignalingR01HL104145 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HARTWIG, JOHN H · 2011 to 2014
$1.6M
Functional and Molecular Dissection of Myeloproliferative Neoplasm Stem CellsK08HL109734 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MULLALLY, ANN · 2011 to 2015
$686k
NHLBI NIH HHS K08 HL109734NHLBI NIH HHS P01 HL059561NHLBI NIH HHS P01 HL107146NHLBI NIH HHS R01 HL089224NHLBI NIH HHS R01 HL104145
6 · The paper itself

Abstract

Dynamins are highly conserved large GTPases (enzymes that hydrolyze guanosine triphosphate) involved in endocytosis and vesicle transport, and mutations in the ubiquitous and housekeeping dynamin 2 (DNM2) have been associated with thrombocytopenia in humans. To determine the role of DNM2 in thrombopoiesis, we generated Dnm2(fl/fl) Pf4-Cre mice specifically lacking DNM2 in the megakaryocyte (MK) lineage. Dnm2(fl/fl) Pf4-Cre mice had severe macrothrombocytopenia with moderately accelerated platelet clearance. Dnm2-null bone marrow MKs had altered demarcation membrane system formation in vivo due to defective endocytic pathway, and fetal liver-derived Dnm2-null MKs formed proplatelets poorly in vitro, showing that DNM2-dependent endocytosis plays a major role in MK membrane formation and thrombopoiesis. Endocytosis of the thrombopoietin receptor Mpl was impaired in Dnm2-null platelets, causing constitutive phosphorylation of the tyrosine kinase JAK2 and elevated circulating thrombopoietin levels. MK-specific DNM2 deletion severely disrupted bone marrow homeostasis, as reflected by marked expansion of hematopoietic stem and progenitor cells, MK hyperplasia, myelofibrosis, and consequent extramedullary hematopoiesis and splenomegaly. Taken together, our data demonstrate that unrestrained MK growth and proliferation results in rapid myelofibrosis and establishes a previously unrecognized role for DNM2-dependent endocytosis in megakaryopoiesis, thrombopoiesis, and bone marrow homeostasis.

Indexed as

EndocytosisThrombopoiesisAnimalsBlood PlateletsBone MarrowDynamin IIGene DeletionMegakaryocytesMiceMice, Inbred C57BLReceptors, ThrombopoietinSignal TransductionSplenomegalyThrombocytopeniaDynamin IIMpl protein, mouseReceptors, Thrombopoietin

Identifiers

PMID25468568
PMCPMC4319232
OpenAlexW2150528960

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.