title: Surface Trafficking of APP and BACE in Live Cells.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Bauereiss
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Welzel
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Grosse-Holz
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lelental
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
authors.affiliation: Institute for Cancer Research, Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Wenzel
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
authors.forename: Teja W
authors.initials: TW
authors.lastname: Groemer
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: APP; BACE; HeLa cells; exocytosis; trafficking pathway; β-secretase