Evidence map›Paper›PMID 33604931›Full record

ArticleThe EMBO journal2021

Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b.

Bilge Ercan, Tomoki Naito, Dylan Hong Zheng Koh, Dennis Dharmawan, Yasunori Saheki

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 2 pooled it
20.9field-weighted citation impact, top 1% 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

46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  6. Review
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  13. Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025
    Review
  14. Article
  15. Article
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  17. TRPV4-dependent CaBiophysical journal · 2024
    Article
  18. Peptide-based allosteric inhibitor targets TNFR1 conformationally active region and disables receptor-ligand signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  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 2 countries.

Bilge ErcanLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID 0000-0002-3780-7946
Tomoki NaitoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID 0000-0002-8393-3601
Dylan Hong Zheng KohLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID 0000-0002-5252-6309
Dennis DharmawanLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Yasunori SahekiLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID 0000-0002-1229-6668
Nanyang Technological University · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesterol is essential for cell physiology. Transport of the "accessible" pool of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) by ER-localized GRAMD1 proteins (GRAMD1a/1b/1c) contributes to cholesterol homeostasis. However, how cells detect accessible cholesterol within the PM remains unclear. We show that the GRAM domain of GRAMD1b, a coincidence detector for anionic lipids, including phosphatidylserine (PS), and cholesterol, possesses distinct but synergistic sites for sensing accessible cholesterol and anionic lipids. We find that a mutation within the GRAM domain of GRAMD1b that is associated with intellectual disability in humans specifically impairs cholesterol sensing. In addition, we identified another point mutation within this domain that enhances cholesterol sensitivity without altering its PS sensitivity. Cell-free reconstitution and cell-based assays revealed that the ability of the GRAM domain to sense accessible cholesterol regulates membrane tethering and determines the rate of cholesterol transport by GRAMD1b. Thus, cells detect the codistribution of accessible cholesterol and anionic lipids in the PM and fine-tune the non-vesicular transport of PM cholesterol to the ER via GRAMD1s.

Indexed as

Amino Acid SubstitutionBiological TransportCell Line, TumorCell MembraneCholesterolEndoplasmic ReticulumGenetic Predisposition to DiseaseHeLa CellsHumansIntellectual DisabilityMembrane ProteinsPhosphatidylserinesPoint MutationProtein DomainsCholesterolGRAMD1B protein, humanMembrane ProteinsPhosphatidylserinescholesterolGRAM domainlipid sensormembrane contact sitesplasma membrane

Identifiers

PMID33604931
PMCPMC7957428
OpenAlexW3130489784

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.