title: The receptor-bound N-terminal ectodomain of the amyloid precursor protein is associated with membrane rafts.
abstract: The soluble N-terminal ectodomain of amyloid precursor protein (sAPP), resulting from alpha-secretase-mediated proteolytic processing, has been shown to function as a growth factor for epithelial cells, including keratinocytes and thyrocytes. Extracellularly applied sAPP binds to a cell surface receptor and exhibits a patchy binding pattern reminiscent of that observed for raft proteins. Here we show that (i) the receptor-bound sAPP resides in a detergent-insoluble membrane microdomain which cofractionates in density gradients with cholesterol-rich membrane rafts and caveolae; (ii) the sAPP-binding microdomains are different from caveolae; and (iii) sAPP is capable of binding to isolated rafts and inducing tyrosine phosphorylation of some raft proteins. These observations suggest that a novel type of membrane raft is involved in sAPP signaling.
authors.affiliation: Institute of Cell Biology and Bonner Forum Biomedizin University of Bonn, Ulrich-Haberland Strasse 61a, D-53121 Bonn, Germany
authors.forename: Ritva
authors.initials: R
authors.lastname: Tikkanen
authors.forename: Ann
authors.initials: A
authors.lastname: Icking
authors.forename: Peter
authors.initials: P
authors.lastname: Beicht
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Waneck
authors.forename: Herzog
authors.initials: H
authors.lastname: Volker
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D021941:Caveolae / Q000378:metabolism; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D003902:Detergents; D004705:Endocytosis / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015603:Keratinocytes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012995:Solubility; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D003902:Detergents; D011994:Recombinant Proteins; D014443:Tyrosine