Cited by 67Genetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and TherapyCellular transport and secretion

Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport With Decreased Life Span and Altered Ubiquitinated-Protein Profiles

Open access
Simonsen, Anne, Cumming, Robert C, Lindmo, Karine, Galaviz, Vanessa, Cheng, Susan, Rusten, Tor Erik, Finley, Kim D·2007·Genetics

Abstract

Defects in lysosomal trafficking pathways lead to decreased cell viability and are associated with progressive disorders in humans. Previously we have found that loss-of-function (LOF) mutations in the Drosophila gene blue cheese (bchs) lead to reduced adult life span, increased neuronal death, and widespread CNS degeneration that is associated with the formation of ubiquitinated-protein aggregates. To identify potential genes that participate in the bchs functional pathway, we conducted a genetic modifier screen based on alterations of an eye phenotype that arises from high-level overexpression of Bchs. We found that mutations in select autophagic and endocytic trafficking genes, defects in cytoskeletal and motor proteins, as well as mutations in the SUMO and ubiquitin signaling pathways behave as modifiers of the Bchs gain-of-function (GOF) eye phenotype. Individual mutant alleles that produced viable adults were further examined for bchs-like phenotypes. Mutations in several lysosomal trafficking genes resulted in significantly decreased adult life spans and several mutants showed changes in ubiquitinated protein profiles as young adults. This work represents a novel approach to examine the role that lysosomal transport and function have on adult viability. The genes characterized in this study have direct human homologs, suggesting that similar defects in lysosomal transport may play a role in human health and age-related processes.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1534/genetics.106.065011

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Simonsen, A., Cumming, R. C., Lindmo, K., Galaviz, V., Cheng, S., Rusten, T. E., & Finley, K. D.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Department of Biochemistry , Center for Cancer Biomedicine, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
Corresponding author
Finley, Kim D
Venue
Genetics
Published
2007-06-01
Volume
176
Issue
2
Pages
1283-1297
ISSN
  • 0016-6731 (ISSN-L)
  • 1943-2631
OpenAlex
W2148013240
Cited by
67
References
61
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 2 · 2013: 6 · 2012: 5
FWCI
1.94
Type
journal article
Language
en
Open access
Locations
  • Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Kreftforeningen
  • Norges Forskningsråd
  • National Institutes of Health
  • National Institute on Aging
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
lysosomal trafficking, genetic modifiers, Drosophila, adult lifespan, ubiquitinated protein aggregates, autophagy, endosomal trafficking, neuronal cell death, ubiquitin signaling, age-related decline
MeSH terms
Animals, DNA Transposable Elements, Drosophila, Larva, Life Expectancy, Mutation, Nerve Degeneration, Nerve Tissue Proteins, Pupa, Gene Expression Regulation, Developmental, Microscopy, Confocal, Protein Transport, Ubiquitin, Drosophila Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review