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.

Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly / Carra, Serena. - (2014). ((Intervento presentato al convegno MOTOR NEURON DISEASES Molecular and Cellular Basis of Selective Vulnerability - FENS satellite event tenutosi a Milano, Italia nel 3-4 Luglio 2014.

Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly

CARRA, Serena
2014

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.
MOTOR NEURON DISEASES Molecular and Cellular Basis of Selective Vulnerability - FENS satellite event
Milano, Italia
3-4 Luglio 2014
Carra, Serena
Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly / Carra, Serena. - (2014). ((Intervento presentato al convegno MOTOR NEURON DISEASES Molecular and Cellular Basis of Selective Vulnerability - FENS satellite event tenutosi a Milano, Italia nel 3-4 Luglio 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1074560
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