title: Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly.
abstract: Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition.
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: S J
authors.initials: SJ
authors.lastname: Seguin
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: F F
authors.initials: FF
authors.lastname: Morelli
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Vinet
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Amore
authors.affiliation: Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Biasi
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Universita' di Milano, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Poletti
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Rubinsztein
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita' di Modena e Reggio Emilia, Modena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Carra
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D012269:Ribosomal Proteins / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; C489092:RPL19 protein, human; D012269:Ribosomal Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein