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The Fate of PrP GPI ‐Anchor Signal Peptide is Modulated by P238S Pathogenic Mutation
Author(s) -
Guizzunti Gianni,
Zurzolo Chiara
Publication year - 2014
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12126
Subject(s) - signal peptide , biology , mutation , microbiology and biotechnology , point mutation , mutant , peptide sequence , peptide , proteasome , cleavage (geology) , receptor , prion protein , genetics , gene , biochemistry , medicine , paleontology , disease , pathology , fracture (geology)
The fate of GPI ‐anchor signal peptides ( GPI‐SPs ) is currently unknown. PrP GPI‐SP shows a remarkable and unusual level of conservation across species and contains two point mutations responsible for genetic cases of prion diseases. Here we show that differently from folate receptor, PrP GPI‐SP is specifically degraded via the proteasome. Furthermore the P238S pathogenic mutation protects the peptide from degradation, leading to its endoplasmic reticulum accumulation. This opens the possibility that PrP GPI‐SP plays a role in neurodegenerative prion diseases.