The beta-amyloid domain is essential for axonal sorting of amyloid precursor protein.
PJ Tienari, B De Strooper, E Ikonen, M Simons, A Weidemann, C Czech, T Hartmann, N Ida, G Multhaup, CL Masters, F Van Leuven, K Beyreuther, CG Dotti
EMBO J | Published : 1996
We have analysed the axonal sorting signals of amyloid precursor protein (APP). Wild-type and mutant versions of human APP were expressed in hippocampal neurons using the Semliki forest virus system. We show that wild-type APP and mutations implicated in Alzheimer's disease and another brain beta-amyloidosis are sorted to the axon. By analysis of deletion mutants we found that the membrane-inserted APP ectodomain but not the cytoplasmic tail is required for axonal sorting. Systematic deletions of the APP ectodomain identified two regions required for axonal delivery: one encoded by exons 11-15 in the carbohydrate domain, the other encoded by exons 16-17 in the juxtamembraneous beta-amyloid d..View full abstract