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Cellular prion protein (PrPC) modulates cell adhesion and signaling in the brain. Conversion to its infectious isoform causes neurodegeneration, including Creutzfeldt-Jakob disease in humans. PrPC undergoes rapid plasma membrane turnover and extracellular release via exosomes. However, the intracellular transport of PrPC and its potential impact on prion disease progression is barely understood. Here we identify critical components of PrPC trafficking that also link intracellular and extracellular PrPC turnover. PrPC associates with muskelin, dynein, and KIF5C at transport vesicles. Notably, muskelin coordinates bidirectional PrPC transport and facilitates lysosomal degradation over exosomal PrPC release. Muskelin gene knockout consequently causes PrPC accumulation at the neuronal surface and on secreted exosomes. Moreover, prion disease onset is accelerated following injection of pathogenic prions into muskelin knockout mice. Our data identify an essential checkpoint in PrPC turnover. They propose a novel connection between neuronal intracellular lysosome targeting and extracellular exosome trafficking, relevant to the pathogenesis of neurodegenerative conditions.
Pubmed ID: 30174115 RIS Download
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This polyclonal secondary targets IgG, Light Chain Specific
View all literature mentionsThis unknown targets Rat IgG (H+L)
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View all literature mentionsThis polyclonal targets IgG (H+L)
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG Control
View all literature mentionsThis unknown targets Murine IgG Control
View all literature mentionsThis polyclonal targets beta-Tubulin III antibody produced in rabbit
View all literature mentionsThis polyclonal targets TRK B
View all literature mentionsThis monoclonal targets TSG101
View all literature mentionsThis monoclonal targets TRPC1 (E-6)
View all literature mentionsThis polyclonal targets PrPC
View all literature mentionsThis polyclonal targets Rab7 antibody produced in rabbit
View all literature mentionsThis polyclonal targets Rab5 antibody produced in rabbit
View all literature mentionsThis polyclonal targets RAB4A
View all literature mentionsThis polyclonal targets Rab11a
View all literature mentionsThis unknown targets
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View all literature mentionsThis monoclonal targets Prion Protein (Clone SAF 84)
View all literature mentionsThis polyclonal targets NMDAR2B antibody
View all literature mentionsThis polyclonal targets MYO6
View all literature mentionsThis unknown targets c-Myc
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal targets Muskelin 1–280
View all literature mentionsThis monoclonal targets Muskelin
View all literature mentionsThis monoclonal targets Mkln1
View all literature mentionsThis polyclonal targets Muskelin
View all literature mentionsThis monoclonal targets LRP1
View all literature mentionsThis monoclonal targets Lamp1
View all literature mentionsThis unknown targets Kinesin 5C
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets Glutamate Receptor 2 (GluR2), aa175-430
View all literature mentionsThis polyclonal targets GFP N-terminal antibody produced in rabbit
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets GABA A Receptor beta 23 Chain extracellular domain of the beta2 & beta3 subunits of the GABA A receptor clone BD17
View all literature mentionsThis monoclonal targets Dynein 74 kDa Intermediate chains cytoplasmic clone 74.1
View all literature mentionsThis monoclonal targets Alzheimer Precursor Protein A4, aa66-81 of APP
View all literature mentionsThis monoclonal targets Adaptin gamma
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus
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Mus musculus with name B6 x STOCK Tyrc-ch Bmp5
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