Evidence map›Paper›PMID 31657721›Full record

ArticleeLife2019

Cholesterol accessibility at the ciliary membrane controls hedgehog signaling.

Maia Kinnebrew, Ellen J Iverson, Bhaven B Patel, Ganesh V Pusapati, Jennifer H Kong, Kristen A Johnson, Giovanni Luchetti, Kaitlyn M Eckert, Jeffrey G McDonald, Douglas F Covey and 3 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

103 citing papers in PubMed, 151 citations in OpenAlex.

  1. Review
  2. Ciliary Membrane Lipid Homeostasis in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  3. Review
  4. Article
  5. Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects.Advances in experimental medicine and biology · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Design principles of ciliary signaling.Journal of cell science · 2025
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

43 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 2 countries.

Maia Kinnebrew *Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.ORCID https://orcid.org/0000-0002-7344-8231
Ellen J Iverson *Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Bhaven B PatelDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Ganesh V PusapatiDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.ORCID https://orcid.org/0000-0002-1406-2566
Jennifer H KongDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Kristen A JohnsonDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.
Giovanni LuchettiDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Kaitlyn M EckertCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States.
Jeffrey G McDonaldDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.
Douglas F CoveyTaylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, United States.
Christian SieboldDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-6635-3621
Arun RadhakrishnanDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.ORCID https://orcid.org/0000-0002-7266-7336
Rajat RohatgiDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.ORCID https://orcid.org/0000-0001-7609-8858
Stanford University · USHumanN (United States) · USThe University of Texas Southwestern Medical Center · USCentre for Human Genetics · GBWashington University in St. Louis · US

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GOLDSTEIN, JOSEPH L · 1985 to 2021
$103.1M
Supplement application for an Olympus automated microscopeR35GM118082 · NIGMS · STANFORD UNIVERSITY · PI RAJAT ROHATGI · 2016 to 2026
$7.6M
Reconstructing Primary CiliaDP2GM105448 · NIGMS · STANFORD UNIVERSITY · PI ROHATGI, RAJAT · 2012 to 2012
$2.4M
Signal Transduction by OxysterolsR01GM106078 · NIGMS · STANFORD UNIVERSITY · PI COVEY, DOUGLAS F, ROHATGI, RAJAT · 2014 to 2017
$1.6M
Molecular mechanisms that regulate target cell sensitivity to Hedgehog morphogensK99GM132518 · NIGMS · STANFORD UNIVERSITY · PI KONG, JENNIFER · 2019 to 2021
$281k
Cancer Research UK 14414Cancer Research UK 26752Cancer Research UK C20724/A14414Cancer Research UK C20724/A26752European Research Council 647278NHLBI NIH HHS P01 HL020948NIGMS NIH HHS DP2 GM105448NIGMS NIH HHS K99 GM132518NIGMS NIH HHS R01 GM106078NIGMS NIH HHS R35 GM118082NIH HHS GM106078NIH HHS GM118082NIH HHS GM13251801NIH HHS HL20948
6 · The paper itself

Abstract

Previously we proposed that transmission of the hedgehog signal across the plasma membrane by Smoothened is triggered by its interaction with cholesterol (Luchetti et al., 2016). But how is cholesterol, an abundant lipid, regulated tightly enough to control a signaling system that can cause birth defects and cancer? Using toxin-based sensors that distinguish between distinct pools of cholesterol, we find that Smoothened activation and Hedgehog signaling are driven by a biochemically-defined, small fraction of membrane cholesterol, termed accessible cholesterol. Increasing cholesterol accessibility by depletion of sphingomyelin, which sequesters cholesterol in complexes, amplifies Hedgehog signaling. Hedgehog ligands increase cholesterol accessibility in the membrane of the primary cilium by inactivating the transporter-like protein Patched 1. Trapping this accessible cholesterol blocks Hedgehog signal transmission across the membrane. Our work shows that the organization of cholesterol in the ciliary membrane can be modified by extracellular ligands to control the activity of cilia-localized signaling proteins.

Indexed as

Signal TransductionAnimalsCholesterolCiliaClustered Regularly Interspaced Short Palindromic RepeatsHedgehog ProteinsHumansCholesterolHedgehog Proteinscell biologycholesteroldevelopmental biologyhedgehog signalingnonepatchedprimary ciliumsignal transductionsmoothened

Identifiers

PMID31657721
PMCPMC6850779
OpenAlexW2982151985

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.