Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal transport with decreased life span and altered ubiquitinated-protein profiles.

Authors: Simonsen A; Cumming RC; Lindmo K; Galaviz V; Cheng S; Rusten TE; Finley KD

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.

Keywords: Animals; DNA Transposable Elements; Drosophila/*genetics/growth & development; Drosophila Proteins/*genetics/*metabolism; Gene Expression Regulation, Developmental; Larva; Life Expectancy; Microscopy, Confocal; Mutation; Nerve Degeneration/genetics; Nerve Tissue Proteins/*genetics/*metabolism; Protein Transport; Pupa; Ubiquitin/*metabolism
Journal: Genetics
Volume: 176
Issue: 2
Pages: 1283-97
Date: April 17, 2007
PMID: 17435236
Select reference article to upload


Citation:

Simonsen A, Cumming RC, Lindmo K, Galaviz V, Cheng S, Rusten TE, Finley KD (2007) Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal transport with decreased life span and altered ubiquitinated-protein profiles. Genetics 176: 1283-97.


Study Lifespan Factors:
  • hk hook
  • bchs blue cheese
  • cm carmine
  • Atg8a Autophagy-related 8a
  • dor deep orange
  • ry rosy
  • car carnation
  • g garnet
  • lt light
  • rb ruby


  • Update (Admin) | Auto-Update

    Comment on This Data Unit