Fly model leads to new model for cellular mechanisms underlying diseases associated with disruption of Valosin-Containing Proteins

Nat Commun. 2021 Jan 21;12(1):513. doi: 10.1038/s41467-020-20796-8.

SVIP is a molecular determinant of lysosomal dynamic stability, neurodegeneration and lifespan.

Johnson AE, Orr BO, Fetter RD, Moughamian AJ, Primeaux LA,
Geier EG, Yokoyama JS, Miller BL, Davis GW
 

From the abstract:

Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson's disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. ... We also establish multiple links between SVIP and VCP-dependent disease in our Drosophila model system. ... Finally, we identify a human SVIP mutation and confirm the pathogenicity of this mutation in our Drosophila model. We propose a model for VCP disease based on the differential, co-factor-dependent recruitment of VCP to intracellular organelles.

DOI: 10.1038/s41467-020-20796-8
PMID: 33479240

Wondering what's IBMPFD? Answer: Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia.