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Full-Text Articles in Medicine and Health Sciences
Unexpected Cell Type-Dependent Effects Of Autophagy On Polyglutamine Aggregation Revealed By Natural Genetic Variation In C. Elegans., J Alexander-Floyd, S Haroon, M Ying, A A Entezari, C Jaeger, M Vermulst, T Gidalevitz
Unexpected Cell Type-Dependent Effects Of Autophagy On Polyglutamine Aggregation Revealed By Natural Genetic Variation In C. Elegans., J Alexander-Floyd, S Haroon, M Ying, A A Entezari, C Jaeger, M Vermulst, T Gidalevitz
Department of Pharmacology and Experimental Therapeutics Faculty Papers
BACKGROUND: Monogenic protein aggregation diseases, in addition to cell selectivity, exhibit clinical variation in the age of onset and progression, driven in part by inter-individual genetic variation. While natural genetic variants may pinpoint plastic networks amenable to intervention, the mechanisms by which they impact individual susceptibility to proteotoxicity are still largely unknown.
RESULTS: We have previously shown that natural variation modifies polyglutamine (polyQ) aggregation phenotypes in C. elegans muscle cells. Here, we find that a genomic locus from C. elegans wild isolate DR1350 causes two genetically separable aggregation phenotypes, without changing the basal activity of muscle proteostasis pathways known to …