Evidence map›Paper›PMID 24088571›Full record

ArticleMolecular biology of the cell2013

Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity.

Amit Tuli, Jerome Thiery, Ashley M James, Xavier Michelet, Mahak Sharma, Salil Garg, Keri B Sanborn, Jordan S Orange, Judy Lieberman, Michael B Brenner

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

49 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
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  6. Translational cancer research · 2025
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  14. Article
  15. Review
  16. Review
  17. Measurement of Lysosome Positioning by Shell Analysis and Line Scan.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  18. Immune Cell Degranulation in Fungal Host Defence.Journal of fungi (Basel, Switzerland) · 2021
    Review
  19. Clinical development of natural killer cells expressing chimeric antigen receptors.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2021
    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

10 authors at 4 institutions in 3 countries.

Amit TuliDivision of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Division of Cell Biology and Immunology, Institute of Microbial Technology, Chandigarh 160036, India Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115 Institut National de la Santé et de la Recherche Médicale, Unité 753, Institut Gustave Roussy, Villejuif 75654, France Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali 140306, India Immunology, Allergy and Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030.
Jerome Thiery
Ashley M James
Xavier Michelet
Mahak Sharma
Salil Garg
Keri B Sanborn
Jordan S Orange
Judy Lieberman
Michael B Brenner
Brigham and Women's Hospital · USBoston Children's Hospital · USBaylor College of Medicine · USUniversity of Pennsylvania · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Directing Function at the Natural Killer Cell Secretory Immunological SynapseR01AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ORANGE, JORDAN SCOTT · 2007 to 2019
$4.8M
T LYMPOHOCYTE RECOGNITIONR01AI028973 · NIAID · DANA-FARBER CANCER INSTITUTE · PI BRENNER, MICHAEL B. · 1990 to 2014
$4.5M
Directing Function at the Natural Killer Cell Secretory Immunological SynapseR37AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jordan Scott Orange · 2024 to 2026
$1.5M
DBT-Wellcome Trust India Alliance IA/I/12/1/500523DBT-Wellcome Trust India Alliance IA/I/14/2/501543NIAID NIH HHS R01 AI028973NIAID NIH HHS R37 AI067946NIGMS NIH HHS T32 GM007753Wellcome Trust
6 · The paper itself

Abstract

Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known as lytic granules, which upon formation of immune synapse with the target cell, polarize toward the immune synapse to deliver their contents to the target cell membrane. Here, we identify a small GTP-binding protein, ADP-ribosylation factor-like 8b (Arl8b), as a critical factor required for NK cell-mediated cytotoxicity. Our findings indicate that Arl8b drives the polarization of lytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. Using a glutathione S-transferase pull-down approach, we identify kinesin family member 5B (KIF5B; the heavy chain of kinesin-1) as an interaction partner of Arl8b from NK cell lysates. Previous studies showed that interaction between kinesin-1 and Arl8b is mediated by SifA and kinesin-interacting protein (SKIP) and the tripartite complex drives the anterograde movement of lysosomes. Silencing of both KIF5B and SKIP in NK cells, similar to Arl8b, led to failure of MTOC-lytic granule polarization to the immune synapse, suggesting that Arl8b and kinesin-1 together control this critical step in NK cell cytotoxicity.

Indexed as

Cytotoxicity, ImmunologicAdaptor Proteins, Signal TransducingADP-Ribosylation FactorsCytoplasmic GranulesExocytosisGene SilencingGTP PhosphohydrolasesHeLa CellsHumansImmunological SynapsesKiller Cells, NaturalKinesinsMicrotubule-Organizing CenterProtein TransportAdaptor Proteins, Signal TransducingADP-Ribosylation FactorsARL8B protein, humanGTP PhosphohydrolasesKinesinsSPHKAP protein, human

Identifiers

PMID24088571
PMCPMC3842998
OpenAlexW1999357986

What Socratic 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 Socratic graph.