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Surface Trafficking of APP and BACE in Live Cells
Author(s) -
Bauereiss Anna,
Welzel Oliver,
Jung Jasmin,
GrosseHolz Simon,
Lelental Natalia,
Lewczuk Piotr,
Wenzel Eva M.,
Kornhuber Johannes,
Groemer Teja W.
Publication year - 2015
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12270
Subject(s) - exocytosis , microbiology and biotechnology , cleavage (geology) , amyloid precursor protein , endosome , cell membrane , peptide , amyloid precursor protein secretase , chemistry , biophysics , cell , secretion , biology , biochemistry , intracellular , alzheimer's disease , medicine , paleontology , disease , pathology , fracture (geology)
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‐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.