title: Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function.
abstract: Stress granules and P bodies are conserved cytoplasmic aggregates of nontranslating messenger ribonucleoprotein complexes (mRNPs) implicated in the regulation of mRNA translation and decay and are related to RNP granules in embryos, neurons, and pathological inclusions in some degenerative diseases. Using baker's yeast, 125 genes were identified in a genetic screen that affected the dynamics of P bodies and/or stress granules. Analyses of such mutants, including CDC48 alleles, provide evidence that stress granules can be targeted to the vacuole by autophagy, in a process termed granulophagy. Moreover, stress granule clearance in mammalian cells is reduced by inhibition of autophagy or by depletion or pathogenic mutations in valosin-containing protein (VCP), the human ortholog of CDC48. Because mutations in VCP predispose humans to amyotrophic lateral sclerosis, frontotemporal lobar degeneration, inclusion body myopathy, and multisystem proteinopathy, this work suggests that autophagic clearance of stress granule related and pathogenic RNP granules that arise in degenerative diseases may be important in reducing their pathology.
authors.affiliation: Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
authors.forename: J Ross
authors.initials: JR
authors.lastname: Buchan
authors.forename: Regina-Maria
authors.initials: RM
authors.lastname: Kolaitis
authors.forename: J Paul
authors.initials: JP
authors.lastname: Taylor
authors.forename: Roy
authors.initials: R
authors.lastname: Parker
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009154:Mutation; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse