Evidence map›Paper›PMID 38506245›Full record

ArticleJournal of cell science2024

MADD regulates natural killer cell degranulation through Rab27a activation.

Michael J Medlyn, Easton Maeder, Claire Bradley, Prasad Phatarpekar, Hyoungjun Ham, Daniel D Billadeau

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
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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

6 authors at 1 institution in 1 country.

Michael J MedlynDepartment of Immunology College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Easton MaederDivision of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0009-0002-9263-9698
Claire BradleyDepartment of Immunology College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Prasad PhatarpekarDivision of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
Hyoungjun HamDivision of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-8669-6875
Daniel D BilladeauDepartment of Immunology College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-2296-9547
Mayo Clinic · US

Funding

PHD TRAINING PROGRAM IN BASIC IMMUNOLOGYT32AI007425 · NIAID · MAYO CLINIC ROCHESTER · PI SHAPIRO, VIRGINIA SMITH · 1995 to 2020
$3.6M
Mechanisms Regulating Human NK Cell CytotoxicityR01AI120949 · NIAID · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D · 2016 to 2020
$2.0M
NIAID NIH HHS R01 AI120949NIAID NIH HHS T32 AI007425NIH HHS R01-AI120949NIH HHS T32 AI07425-25
6 · The paper itself

Abstract

Natural killer (NK) cells have the ability to lyse other cells through the release of lytic granules (LGs). This is in part mediated by the small GTPase Rab27a, which was first identified to play a crucial role in degranulation through the study of individuals harboring mutations in the gene encoding Rab27a. However, the guanine nucleotide exchange factor (GEF) regulating the activation of Rab27a in cytotoxic lymphocytes was unknown. Here, we show that knockout of MADD significantly decreased the levels of GTP-bound Rab27a in both resting and stimulated NK cells, and MADD-deficient NK cells and CD8+ T cells displayed severely reduced degranulation and cytolytic ability, similar to that seen with Rab27a deficiency. Although MADD colocalized with Rab27a on LGs and was enriched at the cytolytic synapse, the loss of MADD did not impact Rab27a association with LGs nor their recruitment to the cytolytic synapse. Together, our results demonstrate an important role for MADD in cytotoxic lymphocyte killing.

Indexed as

ExocytosisMonomeric GTP-Binding ProteinsCD8-Positive T-LymphocytesCell DegranulationDeath Domain Receptor Signaling Adaptor ProteinsGuanine Nucleotide Exchange FactorsHumansKiller Cells, NaturalDeath Domain Receptor Signaling Adaptor ProteinsGuanine Nucleotide Exchange FactorsMADD protein, humanMonomeric GTP-Binding ProteinsCD8+ T cellDegranulationLytic granuleNatural killer cellRab27a

Identifiers

PMID38506245
PMCPMC11058345
OpenAlexW4393005249

What Socratic 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 Socratic graph.