Evidence map›Paper›PMID 21747935›Full record

ArticlePloS one2011

Lipid modifications of Sonic hedgehog ligand dictate cellular reception and signal response.

Vandana K Grover, J Gerardo Valadez, Aaron B Bowman, Michael K Cooper

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Specialized Intercellular Communications via Cytonemes and Nanotubes.Annual review of cell and developmental biology · 2018
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
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  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Lipids and prostate cancer.Prostaglandins & other lipid mediators · 2012
    Review
  20. Targeting protein lipidation in disease.Trends in molecular medicine · 2012
    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

4 authors at 2 institutions in 1 country.

Vandana K GroverDepartment of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
J Gerardo Valadez
Aaron B Bowman
Michael K Cooper
Vanderbilt University Medical Center · USJohn F. Kennedy Center for the Performing Arts · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Gene-Neurotoxicant Interactions in Huntington DiseaseR01ES016931 · NIEHS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOWMAN, AARON B · 2008 to 2018
$4.5M
Shaping a Shh morphogen gradientK02NS053614 · NINDS · VANDERBILT UNIVERSITY · PI COOPER, MICHAEL KANE · 2006 to 2008
$518k
NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NIDDK NIH HHS DK058404NIDDK NIH HHS P30 DK058404NIEHS NIH HHS R01 ES016931NINDS NIH HHS K02 NS053614
6 · The paper itself

Abstract

backgroundSonic hedgehog (Shh) signaling regulates cell growth during embryonic development, tissue homeostasis and tumorigenesis. Concentration-dependent cellular responses to secreted Shh protein are essential for tissue patterning. Shh ligand is covalently modified by two lipid moieties, cholesterol and palmitate, and their hydrophobic properties are known to govern the cellular release and formation of soluble multimeric Shh complexes. However, the influences of the lipid moieties on cellular reception and signal response are not well understood. METHODOLOGY/PRINCIPAL

findingsWe analyzed fully lipidated Shh and mutant forms to eliminate one or both adducts in NIH3T3 mouse embryonic fibroblasts. Quantitative measurements of recombinant Shh protein concentration, cellular localization, and signaling potency were integrated to determine the contributions of each lipid adduct on ligand cellular localization and signaling potency. We demonstrate that lipid modification is required for cell reception, that either adduct is sufficient to confer cellular association, that the cholesterol adduct anchors ligand to the plasma membrane and that the palmitate adduct augments ligand internalization. We further show that signaling potency correlates directly with cellular concentration of Shh ligand. CONCLUSIONS/SIGNIFICANCE: The findings of this study demonstrate that lipid modification of Shh determines cell concentration and potency, revealing complementary functions of hydrophobic modification in morphogen signaling by attenuating cellular release and augmenting reception of Shh protein in target tissues.

Indexed as

Lipid MetabolismSignal TransductionAnimalsCholesterolHedgehog ProteinsHydrophobic and Hydrophilic InteractionsLigandsMiceNIH 3T3 CellsProtein TransportCholesterolHedgehog ProteinsLigands

Identifiers

PMID21747935
PMCPMC3128587
OpenAlexW2027854108

What OpenQuestion holds

Textmetadata
LicenceCC0
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.