Polarisierter Transport des Prion-Proteins

Several proteins linked to neurodegenerative diseases, such as the
-amyloid precursor protein, amyloid -peptide, -secretase, and tau,
undergo selective polarized sorting. We investigated polarized
sorting of the mammalian prion protein (PrPC) and its homologue
doppel (Dpl). In contrast to Dpl, which accumulates on the apical
surface, PrPC is targeted selectively to the basolateral side in
Madin-Darby canine kidney cells. An extensive deletion and domain
swapping analysis revealed that the internal hydrophobic domain
(HD) of PrP (amino acids 113–133) confers basolateral sorting in a
dominant manner. PrP mutants lacking the HD are sorted apically,
while Dpl chimeras containing the HD of PrP are directed to the
basolateral membrane. Furthermore, a pathogenic PrP missense
mutation within the HD leads to aberrant apical sorting of PrP as
well.