Evidence map›Paper›PMID 36904854›Full record

ArticleSensors (Basel, Switzerland)2023

Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells.

Mei C Q Houser, Shane P C Mitchell, Priyanka Sinha, Brianna Lundin, Oksana Berezovska, Masato Maesako

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

Article in Sensors (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
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

6 authors at 1 institution in 1 country.

Mei C Q HouserAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
Shane P C MitchellAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
Priyanka SinhaAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.ORCID 0000-0002-0928-7429
Brianna LundinAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
Oksana BerezovskaAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.
Masato MaesakoAlzheimer's Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital/Harvard Medical School, 114, 16th Street, Charlestown, MA 02129, USA.ORCID 0000-0002-1970-2462
Harvard University · US

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI TANZI, RUDOLPH EMILE · 1998 to 2023
$51.3M
Role of PS1 in neurodegenerationRF1AG044486 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BEREZOVSKA, OKSANA · 2019 to 2019
$3.2M
Role of PS1 in neurodegenerationR01AG044486 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BEREZOVSKA, OKSANA · 2014 to 2018
$2.5M
A unique subpopulation of wild-type neurons recapitulating FAD phenotypesR01AG079838 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Masato Maesako · 2023 to 2026
$2.1M
NIA NIH HHS P01 AG015379NIA NIH HHS R01 AG044486NIA NIH HHS R01 AG079838NIA NIH HHS RF1 AG044486NIH HHS AG 15379NIH HHS AG 44486
6 · The paper itself

Abstract

Our unique multiplexed imaging assays employing FRET biosensors have previously detected that γ-secretase processes APP C99 primarily in late endosomes and lysosomes in live/intact neurons. Moreover we have shown that Aβ peptides are enriched in the same subcellular loci. Given that γ-secretase is integrated into the membrane bilayer and functionally links to lipid membrane properties in vitro, it is presumable that γ-secretase function correlates with endosome and lysosome membrane properties in live/intact cells. In the present study, we show using unique live-cell imaging and biochemical assays that the endo-lysosomal membrane in primary neurons is more disordered and, as a result, more permeable than in CHO cells. Interestingly, γ-secretase processivity is decreased in primary neurons, resulting in the predominant production of long Aβ42 instead of short Aβ38. In contrast, CHO cells favor Aβ38 over the Aβ42 generation. Our findings are consistent with the previous in vitro studies, demonstrating the functional interaction between lipid membrane properties and γ-secretase and provide further evidence that γ-secretase acts in late endosomes and lysosomes in live/intact cells.

Indexed as

Alzheimer DiseaseAmyloid Precursor Protein SecretasesAmyloid beta-PeptidesAnimalsCricetinaeCricetulusEndosomesLipidsLysosomesAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesLipidsAβendosome and lysosomemembrane propertiesγ-secretase

Identifiers

PMID36904854
PMCPMC10007619
OpenAlexW4322630950

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read14
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.