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2015 ; 128
(7
): 1434-43
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The multivesicular body is the major internal site of prion conversion
#MMPMID25663703
Yim YI
; Park BC
; Yadavalli R
; Zhao X
; Eisenberg E
; Greene LE
J Cell Sci
2015[Apr]; 128
(7
): 1434-43
PMID25663703
show ga
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.