Abstract
The amyloid precursor protein (APP) is a type I transmembrane protein with a large ectodomain, a single transmembrane domain and a small cytoplasmic tail (1). Translation of APP occurs at the endoplasmic reticulum (ER) and the protein is translocated into the ER lumen. The N-terminal domain of APP is directed towards the luminal compartment of the ER, whereas the C-terminal domain faces the cytoplasm. After synthesis, APP passes from the ER to the Golgi compartment. APP can then be transported in secretory vesicles to the cell surface, where the large ectodomain faces the extracellular milieu. Cell surface APP can be reinternalized into endosomes and lysosomes (for review see refs. 2 and 3). During its passage through the secretory pathway, APP is subjected to a variety of posttranslational modifications, including proteolytic processing, glycosylation, sulfation, and phosphorylation. Immediately on translocation into the ER, the signal peptide of APP is removed from the N-terminus by signal peptidase. APP is then modified cotranslationally by N-glycosylation on NH2-groups of asparagine residues. After passage into the Golgi compartment, the ectodomain of APP is subjected to O-glycosylation. In late Golgi compartments, e.g., the trans Golgi network, APP is subjected to sulfation on tyrosine residues within its ectodomain (4).
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Walter, J., Haass, C. (2000). Posttranslational Modifications of Amyloid Precursor Protein. In: Hooper, N.M. (eds) Alzheimer's Disease. Methods in Molecular Medicineā¢, vol 32. Humana Press. https://doi.org/10.1385/1-59259-195-7:149
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DOI: https://doi.org/10.1385/1-59259-195-7:149
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