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The most-substantiated role for APP is in synaptic formation and repair; its expression is upregulated during neuronal differentiation and after neural injury.
Roles in cell signaling, long-term potentiation, and cell adhesion have been proposed and supported by as-yet limited research.
It is commonly cleaved by proteases in the secretase family; alpha secretase and beta secretase both remove nearly the entire extracellular domain to release membrane-anchored carboxy-terminal fragments that may be associated with apoptosis.
Cleavage by gamma secretase within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta fragment; gamma secretase is a large multi-subunit complex whose components have not yet been fully characterized, but include presenilin, whose gene has been identified as a major genetic risk factor for Alzheimer's.
In a recent experiment involving transport of peptide-conjugated colored beads, controls were conjugated to a single amino acid, glycine, such that they display the same terminal carboxylic acid group as APP without the intervening 15-amino-acid sequence mentioned above.
The control beads were not motile, which demonstrated that the terminal COOH moiety of peptides is not sufficient to mediate 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.
However, neuronal cell bodies contain less APP as a function of their proximity to amyloid plaques.
(e) Both red and green channels from 100 frames superimposed of the same video as in (c) and (d).
(f) Single bead trajectories at high magnification from a set of superimposed frames showing movements of beads.
(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.