Evidence map›Paper›PMID 26357016›Full record

ArticleeLife2015

The GARP complex is required for cellular sphingolipid homeostasis.

Florian Fröhlich, Constance Petit, Nora Kory, Romain Christiano, Hans-Kristian Hannibal-Bach, Morven Graham, Xinran Liu, Christer S Ejsing, Robert V Farese, Tobias C Walther

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

60 citing papers in PubMed, 120 citations in OpenAlex.

  1. Article
  2. GARP Complex in Golgi Physiology.Sub-cellular biochemistry · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
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  10. Article
  11. Development of a fumonisin-sensitiveApplied and environmental microbiology · 2023
    Article
  12. Article
  13. Role of GARP Vesicle Tethering Complex in Golgi Physiology.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Article
  16. Generation and Analysis of hTERT-RPE1 VPS54 Knock-Out and Rescued Cell Lines.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  17. Article
  18. Article
  19. Article
  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 2 countries.

Florian FröhlichDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Constance PetitDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Nora KoryDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Romain ChristianoDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Hans-Kristian Hannibal-BachDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.
Morven GrahamCenter for Cellular and Molecular Imaging, Yale School of Medicine, New Haven, United States.
Xinran LiuCenter for Cellular and Molecular Imaging, Yale School of Medicine, New Haven, United States.
Christer S EjsingDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.
Robert V FareseDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Tobias C WaltherDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
Harvard University · USBroad Institute · USUniversity of Southern Denmark · DKYale University · US

Funding

Cellular Functions of Plasma Membrane Organization by EisosomesR01GM095982 · NIGMS · YALE UNIVERSITY · PI WALTHER, TOBIAS C · 2012 to 2015
$1.2M
NIGMS NIH HHS R01 GM095982NIGMS NIH HHS R01GM095982
6 · The paper itself

Abstract

Sphingolipids are abundant membrane components and important signaling molecules in eukaryotic cells. Their levels and localization are tightly regulated. However, the mechanisms underlying this regulation remain largely unknown. In this study, we identify the Golgi-associated retrograde protein (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many of the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2.

Indexed as

HomeostasisHeLa CellsHumansMembrane ProteinsSaccharomyces cerevisiaeSphingolipidsLRRC32 protein, humanMembrane ProteinsSphingolipidscell biologyGARP complexhomeostasishumanneurodegenerationPCCA2retrograde endosome to Golgi transportS. cerevisiaesphingolipid metabolism

Identifiers

PMID26357016
PMCPMC4600884
OpenAlexW2127683408

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.