Evidence map›Paper›PMID 22272187›Full record

ArticlePLoS biology2012

Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells.

Nan Lu, Qian Shen, Timothy R Mahoney, Lukas J Neukomm, Ying Wang, Zheng Zhou

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Worms, Fat, and Death:Metabolites · 2021
    Review
  14. Article
  15. Article
  16. The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  17. Review
  18. Autophagy in C. elegans development.Developmental biology · 2019
    Review
  19. Multiple Aspects of PIP2 Involvement inInternational journal of molecular sciences · 2018
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Nan LuVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Qian Shen
Timothy R Mahoney
Lukas J Neukomm
Ying Wang
Zheng Zhou
Baylor College of Medicine · USUniversity of Zurich · CH

Funding

Research Education and Career Horizons ProgramK12GM084897 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI SIFERS, RICHARD NORMAN, SLAUGHTER, GAYLE · 2008 to 2016
$8.3M
Recognition of Apoptotic Cells for Their PhagocytosisR01GM067848 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI ZHOU, ZHENG · 2003 to 2021
$5.7M
Mutidisciplinary Training;Brain Disorders &DevelopmentT32NS043124 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI SWANN, JOHN WILLIAM · 2002 to 2021
$4.6M
NIGMS NIH HHS GM067848NIGMS NIH HHS K12 GM084897NIGMS NIH HHS K12-GM084897-03NIGMS NIH HHS R01 GM067848NINDS NIH HHS T32 NS043124NINDS NIH HHS T32-NS043124
6 · The paper itself

Abstract

Phosphatidylinositol 3-phosphate (PtdIns(3)P) is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3)P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K) Vps34 is regarded as the only kinase that produces PtdIns(3)P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3)P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3)P in a manner dependent on the large GTPase dynamin (DYN-1). PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3)P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3)P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3)P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3)P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3)P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.

Indexed as

ApoptosisAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsDown-RegulationEnzyme ActivationPhagosomesPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoprotein PhosphatasesProtein Bindingrab GTP-Binding ProteinsCaenorhabditis elegans ProteinsPhosphatidylinositol 3-Kinasesphosphatidylinositol 3-phosphatePhosphatidylinositol PhosphatesPhosphoprotein Phosphatasesrab GTP-Binding Proteins

Identifiers

PMID22272187
PMCPMC3260314
OpenAlexW2029716305

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.