Evidence map›Paper›PMID 32065241›Full record

ArticleCellular and molecular life sciences : CMLS2020

The Rab5 activator RME-6 is required for amyloid precursor protein endocytosis depending on the YTSI motif.

Simone Eggert, Tomas Gruebl, Ritu Rajender, Carsten Rupp, Bianca Sander, Amelie Heesch, Marius Zimmermann, Sebastian Hoepfner, Hanswalter Zentgraf, Stefan Kins

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

10 authors at 3 institutions in 2 countries.

Simone EggertDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Tomas GrueblDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Ritu RajenderDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Carsten RuppDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Bianca SanderDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Amelie HeeschDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Marius ZimmermannDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
Sebastian HoepfnerMPI of Molecular Cell Biology and Genetics, Dresden, Germany.
Hanswalter ZentgrafDKFZ, Heidelberg, Germany.
Stefan KinsDepartment of Human Biology and Human Genetics, Technical University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany. s.kins@biologie.uni-kl.de.ORCID http://orcid.org/0000-0002-7231-4872
University of Kaiserslautern · DEHeidelberg University · DEMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endocytosis of the amyloid precursor protein (APP) is critical for generation of β-amyloid, aggregating in Alzheimer's disease. APP endocytosis depending on the intracellular NPTY motif is well investigated, whereas involvement of the YTSI (also termed BaSS) motif remains controversial. Here, we show that APP lacking the YTSI motif (ΔYTSI) displays reduced localization to early endosomes and decreased internalization rates, similar to APP ΔNPTY. Additionally, we show that the YTSI-binding protein, PAT1a interacts with the Rab5 activator RME-6, as shown by several independent assays. Interestingly, knockdown of RME-6 decreased APP endocytosis, whereas overexpression increased the same. Similarly, APP ΔNPTY endocytosis was affected by PAT1a and RME-6 overexpression, whereas APP ΔYTSI internalization remained unchanged. Moreover, we could show that RME-6 mediated increase of APP endocytosis can be diminished upon knocking down PAT1a. Together, our data identify RME-6 as a novel player in APP endocytosis, involving the YTSI-binding protein PAT1a.

Indexed as

Alzheimer DiseaseAmino Acid MotifsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCarrier ProteinsEndocytosisEndosomesHumansMiceProtein Transportrab5 GTP-Binding ProteinsTransport VesiclesAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCarrier Proteinsrab5 GTP-Binding ProteinsBasolateral sorting signalClathrin-dependent endocytosisGDP–GTP exchange factorProtein interacting with APP tail 1SortingTrafficking

Identifiers

PMID32065241
PMCPMC7671991
OpenAlexW3006242556

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.