Evidence map›Paper›PMID 28035045›Full record

ArticleMolecular biology of the cell2017

Multiphasic dynamics of phosphatidylinositol 4-phosphate during phagocytosis.

Roni Levin, Gerald R V Hammond, Tamas Balla, Pietro De Camilli, Gregory D Fairn, Sergio Grinstein

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  12. An update on genetically encoded lipid biosensors.Molecular biology of the cell · 2022
    Article
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  14. Review
  15. Review
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  17. Examining the Underappreciated Role ofFrontiers in immunology · 2021
    Review
  18. Review
  19. Review
  20. Review
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 5 institutions in 2 countries.

Roni LevinDivision of Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Gerald R V HammondDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.
Tamas BallaProgram in Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Pietro De CamilliDepartments of Neuroscience and Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, Yale University Medical School, New Haven, CT 06510.
Gregory D FairnDepartment of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Sergio GrinsteinDivision of Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada sergio.grinstein@sickkids.ca.
St. Michael's Hospital · CAHoward Hughes Medical Institute · USNational Institutes of Health · USUniversity of Pittsburgh · USUniversity of Toronto · CA

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Phosphoinositide-calcium Signaling In Cell RegulationZIAHD000196 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BALLA, TAMAS · 2009 to 2025
$26.3M
OCRL and the pathogenesis of Lowe Syndrome and Dent DiseaseR01DK082700 · NIDDK · YALE UNIVERSITY · PI DE CAMILLI, PIETRO · 2009 to 2016
$2.4M
CIHR FDN-143202CIHR MOP-133656Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001863NIDDK NIH HHS R01 DK082700
6 · The paper itself

Abstract

We analyzed the distribution, fate, and functional role of phosphatidylinositol 4-phosphate (PtdIns4P) during phagosome formation and maturation. To this end, we used genetically encoded probes consisting of the PtdIns4P-binding domain of the bacterial effector SidM. PtdIns4P was found to undergo complex, multiphasic changes during phagocytosis. The phosphoinositide, which is present in the plasmalemma before engagement of the target particle, is transiently enriched in the phagosomal cup. Soon after the phagosome seals, PtdIns4P levels drop precipitously due to the hydrolytic activity of Sac2 and phospholipase C, becoming undetectable for ∼10 min. PtdIns4P disappearance coincides with the emergence of phagosomal PtdIns3P. Conversely, the disappearance of PtdIns3P that signals the transition from early to late phagosomes is accompanied by resurgence of PtdIns4P, which is associated with the recruitment of phosphatidylinositol 4-kinase 2A. The reacquisition of PtdIns4P can be prevented by silencing expression of the kinase and can be counteracted by recruitment of a 4-phosphatase with a heterodimerization system. Using these approaches, we found that the secondary accumulation of PtdIns4P is required for proper phagosomal acidification. Defective acidification may be caused by impaired recruitment of Rab7 effectors, including RILP, which were shown earlier to displace phagosomes toward perinuclear lysosomes. Our results show multimodal dynamics of PtdIns4P during phagocytosis and suggest that the phosphoinositide plays important roles during the maturation of the phagosome.

Indexed as

1-Phosphatidylinositol 4-KinaseAnimalsEndosomesLysosomesMacrophagesMiceMinor Histocompatibility AntigensPhagocytosisPhagosomesPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)rab GTP-Binding ProteinsRAW 264.7 Cells1-Phosphatidylinositol 4-KinaseMinor Histocompatibility AntigensPhosphatidylinositol 3-Kinasesphosphatidylinositol 3-phosphatephosphatidylinositol 4-phosphatephosphatidylinositol phosphate 4-kinasePhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)PI4KIIIalpha protein, humanrab GTP-Binding Proteins

Identifiers

PMID28035045
PMCPMC5221617
OpenAlexW2550424949

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.