Evidence map›Paper›PMID 25551774›Full record

ArticleAutophagy2014

Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion.

Hemma Brandstaetter, Chieko Kishi-Itakura, David A Tumbarello, Dietmar J Manstein, Folma Buss

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 8% 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

48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

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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

5 authors at 3 institutions in 3 countries.

Hemma Brandstaettera Cambridge Institute for Medical Research ; University of Cambridge ; Cambridge , UK.
Chieko Kishi-Itakura
David A Tumbarello
Dietmar J Manstein
Folma Buss
University of Cambridge · GBInstitute for Medical Research · MYMedizinische Hochschule Hannover · DE

Funding

Medical Research Council MR/K000888/1Wellcome Trust 100140
6 · The paper itself

Abstract

MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.

Indexed as

AutophagyCell LineCell MovementEndocytosisEndosomesHumansLysosomesMembrane FusionMembrane MicrodomainsMyosinsMyosin Type IPhagosomesProtein TransportMYO1C protein, humanMyosinsMyosin Type IautophagyBafA1, bafilomycin A1cholesterolEGF, epidermal growth factorEGFR, epidermal growth factor receptorelectron microscopyEM, electron microscopyGFP, green fluorescent proteinKD, knockdownLAMP1, lysosomal-associated membrane protein 1LC3, microtubule-associated protein 1 light chain 3lipid raftlysosome, MYO1CMVB, multivesicular bodyMYO1C, myosin ICPB, phosphate bufferPCIP, pentachloropseudilinPtdIns(4, 5)P2, phosphatidylinositol 4, 5-bisphosphateRFP, red fluorescent proteinRPE, retinal pigment epithelium

Identifiers

PMID25551774
PMCPMC4502697
OpenAlexW2094697438

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.