title: The multivesicular body is the major internal site of prion conversion.
abstract: The conversion of the properly folded prion protein, PrPc, to its misfolded amyloid form, PrPsc, occurs as the two proteins traffic along the endocytic pathway and PrPc is exposed to PrPsc. To determine the specific site of prion conversion, we knocked down various proteins in the endocytic pathway including Rab7a, Tsg101 and Hrs (also known as HGS). PrPsc was markedly reduced in two chronically infected cell lines by preventing the maturation of the multivesicular body, a process that begins in the early endosome and ends with the sorting of cargo to the lysosome. By contrast, knocking down proteins in the retromer complex, which diverts cargo away from the multivesicular body caused an increase in PrPsc levels. These results suggest that the multivesicular body is the major site for intracellular conversion of PrPc to PrPsc.
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA.
authors: Yang-In
authors: YI
authors: Yim
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA.
authors: Bum-Chan
authors: BC
authors: Park
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA.
authors: Rajgopal
authors: R
authors: Yadavalli
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA.
authors: Xiaohong
authors: X
authors: Zhao
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA.
authors: Evan
authors: E
authors: Eisenberg
authors: Laboratory of Cell Biology, NHLBI, NIH, Bethesda, MD 20892, USA greenel@helix.nih.gov.
authors: Lois E
authors: LE
authors: Greene
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D057146:Multivesicular Bodies / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions
keywords: Conversion; Multivesicular body; Prion; Scrapie