Evidence map›Paper›PMID 18188447›Full record

ArticleThe Journal of clinical investigation2008

Loss of PIP5KIgamma, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes.

Yanfeng Wang, Rustem I Litvinov, Xinsheng Chen, Tami L Bach, Lurong Lian, Brian G Petrich, Susan J Monkley, Yasunori Kanaho, David R Critchley, Takehiko Sasaki and 4 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

49 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
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  11. Actin cytoskeleton in mesenchymal-to-amoeboid transition of cancer cells.International review of cell and molecular biology · 2020
    Review
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  17. Review
  18. Article
  19. Article
  20. Involvement of Membrane Blebbing in Immunological Disorders and Cancer.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2016
    Review
4 · The record

Corrections and comments

  • Erratum issued
    Kanaho, Yasunori [added]
5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Yanfeng WangDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Rustem I Litvinov
Xinsheng Chen
Tami L Bach
Lurong Lian
Brian G Petrich
Susan J Monkley
Yasunori Kanaho
David R Critchley
Takehiko Sasaki
Morris J Birnbaum
John W Weisel
John Hartwig
Charles S Abrams
University of Pennsylvania · USUniversity of Leicester · GBBrigham and Women's Hospital · US

Funding

Wellcome Trust
6 · The paper itself

Abstract

Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is an abundant phospholipid that contributes to second messenger formation and has also been shown to contribute to the regulation of cytoskeletal dynamics in all eukaryotic cells. Although the alpha, beta, and gamma isoforms of phosphatidylinositol-4-phosphate-5-kinase I (PIP5KI) all synthesize PIP2, mammalian cells usually contain more than one PIP5KI isoform. This raises the question of whether different isoforms of PIP5KI fulfill different functions. Given the speculated role of PIP(2) in platelet and megakaryocyte actin dynamics, we analyzed murine megakaryocytes lacking individual PIP5KI isoforms. PIP5KIgamma(-/-) megakaryocytes exhibited plasma membrane blebbing accompanied by a decreased association of the membrane with the cytoskeleton. This membrane defect was rescued by adding back wild-type PIP5KIgamma, but not by adding a catalytically inactive mutant or a splice variant lacking the talin-binding motif. Notably, both PIP5KIbeta- and PIP5KIgamma(-/-) cells had impaired PIP(2) synthesis. However, PIP5KIbeta-null cells lacked the membrane-cytoskeleton defect. Furthermore, overexpressing PIP5KIbeta in PIP5KIgamma(-/-) cells failed to revert this defect. Megakaryocytes lacking the PIP5KIgamma-binding partner, talin1, mimicked the membrane-cytoskeleton defect phenotype seen in PIP5KIgamma(-/-) cells. These findings demonstrate a unique role for PIP5KIgamma in the anchoring of the cell membrane to the cytoskeleton in megakaryocytes, probably through a pathway involving talin. These observations further demonstrate that individual PIP5KI isoforms fulfill distinct functions within cells.

Indexed as

AnimalsCell MembraneCytoskeletonMaleMegakaryocytesMiceMice, Mutant StrainsPhosphatidylinositol 4,5-DiphosphatePhosphotransferases (Alcohol Group Acceptor)Protein IsoformsTalin1-phosphatidylinositol-4-phosphate 5-kinasePhosphatidylinositol 4,5-DiphosphatePhosphotransferases (Alcohol Group Acceptor)Protein IsoformsTalin

Identifiers

PMID18188447
PMCPMC2176194
OpenAlexW2042341077

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.