Evidence map›Paper›PMID 39813120›Full record

ArticleCell reports2025

The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.

Luis A Pedroza, Frederique van den Haak, Alexander Frumovitz, Evelyn Hernandez, Everardo Hegewisch-Solloa, Tabitha K Orange, Keri B Sheehan, Susan Prockop, Aaron Bodansky, Ivan K Chinn and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

15 authors.

Luis A PedrozaVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Frederique van den HaakVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Alexander FrumovitzVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Evelyn HernandezVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Everardo Hegewisch-SolloaVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Tabitha K OrangeVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Keri B SheehanGE HealthCare, Marlborough, MA 01752, USA.
Susan ProckopBoston Children's Hospital, Boston, MA 02115, USA.
Aaron BodanskyDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Ivan K ChinnDepartment of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
James R LupskiDepartment of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Emily M MaceVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Yu LiVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Jordan S OrangeVagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: jso2121@cumc.columbia.edu.

Funding

Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Frequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohortU01HG011758 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI RICHARD A GIBBS, JAMES R. LUPSKI · 2021 to 2026
$13.8M
GENETIC, IMMUNOLOGIC AND MECHANISTIC BASIS OF HUMAN NK CELL DEFICIENCYR01AI120989 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ORANGE, JORDAN SCOTT · 2016 to 2025
$7.7M
Directing Function at the Natural Killer Cell Secretory Immunological SynapseR01AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ORANGE, JORDAN SCOTT · 2007 to 2019
$4.8M
Directing Function at the Natural Killer Cell Secretory Immunological SynapseR37AI067946 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jordan Scott Orange · 2024 to 2026
$1.5M
NHGRI NIH HHS U01 HG011758NHGRI NIH HHS UM1 HG006542NIAID NIH HHS R01 AI067946NIAID NIH HHS R01 AI120989NIAID NIH HHS R37 AI067946
6 · The paper itself

Abstract

Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion. We identify unappreciated intimate relationships between the Golgi, MTOC, and LGs after cytotoxic cell activation, as well as the trans-Golgin protein GCC2 on the LG surface. GCC2 serves to tether LGs to the Golgi following convergence, and both GCC2 and the Golgi are required for the persistence of convergence. GCC2 allows LGs to utilize the Golgi as a docking station preventing LG dispersion and innocent bystander killing in complex three-dimensional environments. We also identify GCC2 variants causing human natural killer cell deficiency, further emphasizing the importance of LG convergence and Golgi linkage in precision targeting for human immunity.

Indexed as

Cytoplasmic GranulesCytotoxicity, ImmunologicGolgi ApparatusKiller Cells, NaturalGolgi Matrix ProteinsHumansMicrotubule-Organizing CenterGolgi Matrix Proteinscancerconfocal microscopyCP: ImmunologycytotoxicityGCC2GolgiGolginslytic granule convergencenatural killer cells

Identifiers

PMID39813120
PMCPMC11844255

What OpenQuestion holds

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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.