Evidence map›Paper›PMID 28265073›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

SM protein Munc18-2 facilitates transition of Syntaxin 11-mediated lipid mixing to complete fusion for T-lymphocyte cytotoxicity.

Waldo A Spessott, Maria L Sanmillan, Margaret E McCormick, Vineet V Kulkarni, Claudio G Giraudo

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.8field-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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. UNCP-18 is amicroPublication biology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. CD8Advances in experimental medicine and biology · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Schizophrenia-Linked Protein tSNARE1 Regulates Endosomal Trafficking in Cortical Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Frontiers in immunology · 2020
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

5 authors at 1 institution in 1 country.

Waldo A SpessottDivision of Cell Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania-Children's Hospital of Philadelphia, Philadelphia PA 19104.
Maria L SanmillanDivision of Cell Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania-Children's Hospital of Philadelphia, Philadelphia PA 19104.
Margaret E McCormickDivision of Cell Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania-Children's Hospital of Philadelphia, Philadelphia PA 19104.
Vineet V KulkarniDivision of Cell Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania-Children's Hospital of Philadelphia, Philadelphia PA 19104.
Claudio G GiraudoDivision of Cell Pathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania-Children's Hospital of Philadelphia, Philadelphia PA 19104; giraudoc@mail.med.upenn.edu.ORCID 0000-0002-9124-2229
Children's Hospital of Philadelphia · US

Funding

Role of Stx11 and STXBP2 in lytic granule exocytosis in health and diseaseR01AI123538 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI GIRAUDO, CLAUDIO GUILLERMO · 2017 to 2021
$2.1M
Exocytosis of Lytic granulesR01GM123020 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI GIRAUDO, CLAUDIO GUILLERMO · 2017 to 2021
$1.6M
NIAID NIH HHS R01 AI123538NIGMS NIH HHS R01 GM123020
6 · The paper itself

Abstract

The atypical lipid-anchored Syntaxin 11 (STX11) and its binding partner, the Sec/Munc (SM) protein Munc18-2, facilitate cytolytic granule release by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Patients carrying mutations in these genes develop familial hemophagocytic lymphohistiocytosis, a primary immunodeficiency characterized by impaired lytic granule exocytosis. However, whether a SNARE such as STX11, which lacks a transmembrane domain, can support membrane fusion in vivo is uncertain, as is the precise role of Munc18-2 during lytic granule exocytosis. Here, using a reconstituted "flipped" cell-cell fusion assay, we show that lipid-anchored STX11 and its cognate SNARE proteins mainly support exchange of lipids but not cytoplasmic content between cells, resembling hemifusion. Strikingly, complete fusion is stimulated by addition of wild-type Munc18-2 to the assay, but not of Munc18-2 mutants with abnormal STX11 binding. Our data reveal that Munc18-2 is not just a chaperone of STX11 but also directly contributes to complete membrane merging by promoting SNARE complex assembly. These results further support the concept that SM proteins in general are part of the core fusion machinery. This fusion mechanism likely contributes to other cell-type-specific exocytic processes such as platelet secretion.

Indexed as

Cytotoxicity, ImmunologicMembrane Fusion3T3 CellsAnimalsCarrier ProteinsCHO CellsCricetulusHumansKiller Cells, NaturalMembrane LipidsMiceMultiprotein ComplexesMunc18 ProteinsProtein BindingProtein Interaction Domains and MotifsQa-SNARE ProteinsCarrier ProteinsMembrane LipidsMultiprotein ComplexesMunc18 ProteinsQa-SNARE ProteinsSNARE ProteinsCTLMunc18-2SM proteinSNARESyntaxin 11

Identifiers

PMID28265073
PMCPMC5358394
OpenAlexW2591874679

What OpenQuestion 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 OpenQuestion graph.