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Surface Trafficking of APP and BACE in Live Cells.

ABSTRACT: Amyloid-? (A?)-peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of A? precursor protein (APP) by ?-site APP-cleaving enzyme (BACE). Using live-cell imaging of APP and BACE labeled with pH-sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by ?-secretase on the cellular surface after exocytosis. Furthermore, simultaneous dual-color evanescent field illumination revealed that the two proteins are trafficked to the surface in separate compartments. Perturbing the membrane lipid composition resulted in a reduced frequency of exocytosis and affected BACE more strongly than APP. We propose that surface fusion frequency is a key factor regulating the aggregation of APP and BACE in the same membrane compartment and that this process can be modulated via pharmacological intervention.

SUBMITTER: Bauereiss A

PROVIDER: S-EPMC6680167 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Surface Trafficking of APP and BACE in Live Cells.

Bauereiss Anna A Welzel Oliver O Jung Jasmin J Grosse-Holz Simon S Lelental Natalia N Lewczuk Piotr P Wenzel Eva M EM Kornhuber Johannes J Groemer Teja W TW

Traffic (Copenhagen, Denmark) 20150414 6

Amyloid-β (Aβ)-peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of Aβ precursor protein (APP) by β-site APP-cleaving enzyme (BACE). Using live-cell imaging of APP and BACE labeled with pH-sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by α-secretase on the cellular surface after exocytosis. Furthermore, simultaneous dual-colo ...[more]

PMID: 25712587

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