The role of cholesterol in lipid raft maintenance has been cited as a likely explanation for observations that high cholesterol and apolipoprotein E genotype are major risk factors for Alzheimer's disease.Although the native biological role of APP is of obvious interest to Alzheimer's research, thorough understanding has remained elusive.The extracellular region, much larger than the intracellular region, is divided into the E1 and E2 domains, linked by an acidic domain (Ac D); E1 contains two subdomains including a growth factor-like domain (GFLD) and a copper-binding domain (Cu BD) interacting tightly together.APP undergoes extensive post-translational modification including glycosylation, phosphorylation, sialylation, and tyrosine sulfation, as well as many types of proteolytic processing to generate peptide fragments.
This is accomplished via fast anterograde transport.
It has been found that APP can mediate interaction between cargo and kinesin and thus facilitate this transport.
Specifically, a short peptide 15-amino-acid sequence from the cytoplasmic carboxy-terminus is necessary for interaction with the motor protein.
(a) A low magnification image immediately after co-injection of red negatively charged and green glycine-conjugated beads showing the injection site, marked with an oil droplet, appearing as a round yellow sphere.
Overlap of red and green fluorescence produces a yellow image.
(e) Both red and green channels from 100 frames superimposed of the same video as in (c) and (d).