Evidence map›Paper›PMID 29030399›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018

Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation.

Néstor Más Gómez, Wennan Lu, Jason C Lim, Kirill Kiselyov, Keith E Campagno, Yulia Grishchuk, Susan A Slaugenhaupt, Bruce A Pfeffer, Steven J Fliesler, Claire H Mitchell

Open access · bronzeAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.6field-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

32 citing papers in PubMed, 48 citations in OpenAlex.

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  11. TheFrontiers in cell and developmental biology · 2022
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  19. The cell biology of the retinal pigment epithelium.Progress in retinal and eye research · 2020
    Review
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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 6 institutions in 2 countries.

Néstor Más GómezDepartment of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Wennan LuDepartment of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jason C LimDepartment of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kirill KiselyovDepartment of Biological Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Keith E CampagnoDepartment of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Yulia GrishchukCenter for Genomic Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, USA.
Susan A SlaugenhauptCenter for Genomic Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, USA.
Bruce A PfefferDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York (SUNY)-University at Buffalo, Buffalo, New York, USA.
Steven J FlieslerDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York (SUNY)-University at Buffalo, Buffalo, New York, USA.
Claire H MitchellDepartment of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
University of Pennsylvania · USCenter for Genomic Science · ITHarvard University · USUniversity at Buffalo, State University of New York · USUniversity of Pittsburgh · USVA Western New York Healthcare System · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
ISOPRENOID METABOLISM IN THE RETINAR01EY007361 · NEI · UNIVERSITY OF SOUTH FLORIDA · PI FLIESLER, STEVEN J. · 1988 to 2015
$4.4M
NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY007361NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY015537
6 · The paper itself

Abstract

The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a conduit for lysosomal calcium efflux, and channel activity may be affected by lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are particularly susceptible to build-up of lysosomal waste products because they must degrade the outer segments phagocytosed daily from adjacent photoreceptors; incomplete degradation leads to accumulation of lipid waste in lysosomes. This study asks whether stimulation of TRPML1 can release lysosomal calcium in RPE cells and whether such release is affected by lysosomal accumulations. The TRPML agonist ML-SA1 raised cytoplasmic calcium levels in mouse RPE cells, hesRPE cells, and ARPE-19 cells; this increase was rapid, robust, reversible, and reproducible. The increase was not altered by extracellular calcium removal or by thapsigargin but was eliminated by lysosomal rupture with glycyl-l-phenylalanine-β-naphthylamide. Treatment with desipramine to inhibit acid sphingomyelinase or YM201636 to inhibit PIKfyve also reduced the cytoplasmic calcium increase triggered by ML-SA1, whereas RPE cells from TRPML1

Indexed as

Calcium SignalingLipid MetabolismAnimalsCalciumCell LineDisease Models, AnimalHumansLysosomesMacular DegenerationMiceMice, KnockoutPhthalimidesQuinolinesRetinal Pigment EpitheliumStargardt DiseaseTransient Receptor Potential ChannelsCalciumMCOLN1 protein, humanMcoln1 protein, mouseML-SA1 compoundPhthalimidesQuinolinesTransient Receptor Potential Channelscalcium signalingcellular aginglysosomal storage diseasemucolipinRPE

Identifiers

PMID29030399
PMCPMC5888396
OpenAlexW2762908328

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.