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- Title
Lack of N-glycosylation increases amyloidogenic processing of the amyloid precursor protein.
- Authors
Lin, Tong; Husen, Lea S van; Yu, Yang; Tjernberg, Lars O; Schedin-Weiss, Sophia
- Abstract
The amyloid precursor protein (APP) is a ubiquitously expressed type 1 transmembrane protein mostly known for serving as a precursor to the amyloid-β peptide (Aβ), a culprit in Alzheimer disease (AD). However, APP also has important physiological functions by being implicated in, for instance, adhesion, signaling, neuronal development, and synaptic function. Human APP contains 2 N-glycosylation sites, at asparagine (N) 467 (N467) and N496. Here, we studied the role of N-glycosylation on APP trafficking and processing by constructing APP-SNAP plasmid vectors for wildtype APP and N-glycosylation site mutants in which N467 or N496 was replaced by glutamine (Q) and expressed these in HEK293T cells. Lack of either of the 2 N -glycans resulted in a reduction in the size of intracellular APP-SNAP-positive vesicles and a reduction of APP-SNAP in the plasma membrane and lysosomes. Importantly, loss of either of the 2 N -glycans resulted in elevated levels of intracellular as well as secreted Aβ42. These data suggest that N -glycans have a major impact on trafficking and processing of APP and could play an important role in the development of AD.
- Subjects
AMYLOID beta-protein precursor; GLYCANS; MEMBRANE proteins; PEPTIDES; ALZHEIMER'S disease; CELL membranes; LYSOSOMES
- Publication
Glycobiology, 2022, Vol 32, Issue 6, p506
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cwac009