NR ARUA
AU Uelhoff,A.; Tatzelt,J.; Aguzzi,A.; Winklhofer,K.F.; Haass,C.
TI A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein
QU The Journal of Biological Chemistry 2005 Feb 18; 280(7): 5137-40
PT journal article
AB Several proteins linked to neurodegenerative diseases, such as the beta-amyloid precursor protein, amyloid beta-peptide, beta-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.
MH Animals; Cell Line; *Cell Polarity; Chimeric Proteins/chemistry/genetics/metabolism; Dogs; Hydrophobicity; Mice; Mutation/*genetics; Prion Diseases/*genetics; Prions/chemistry/genetics/*metabolism; Protein Sorting Signals/physiology; Protein Structure, Tertiary; Protein Transport; Research Support, Non-U.S. Gov't; Sequence Deletion/genetics
AD Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany.
SP englisch
PO USA