title: Amyloid precursor protein is an autonomous growth cone adhesion molecule engaged in contact guidance.
abstract: Amyloid precursor protein (APP), a transmembrane glycoprotein, is well known for its involvement in the pathogenesis of Alzheimer disease of the aging brain, but its normal function is unclear. APP is a prominent component of the adult as well as the developing brain. It is enriched in axonal growth cones (GCs) and has been implicated in cell adhesion and motility. We tested the hypothesis that APP is an extracellular matrix adhesion molecule in experiments that isolated the function of APP from that of well-established adhesion molecules. To this end we plated wild-type, APP-, or β1-integrin (Itgb1)- misexpressing mouse hippocampal neurons on matrices of either laminin, recombinant L1, or synthetic peptides binding specifically to Itgb1 s or APP. We measured GC adhesion, initial axonal outgrowth, and substrate preference on alternating matrix stripes and made the following observations: Substrates of APP-binding peptide alone sustain neurite outgrowth; APP dosage controls GC adhesion to laminin and APP-binding peptide as well as axonal outgrowth in Itgb1- independent manner; and APP directs GCs in contact guidance assays. It follows that APP is an independently operating cell adhesion molecule that affects the GC's phenotype on APP-binding matrices including laminin, and that it is likely to affect axon pathfinding in vivo.
authors.affiliation: Department of Pediatrics and Colorado Intellectual and Developmental Disabilities Research Center, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Sosa
authors.forename: Jared
authors.initials: J
authors.lastname: Bergman
authors.forename: Adriana
authors.initials: A
authors.lastname: Estrada-Bernal
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Glorioso
authors.forename: John M
authors.initials: JM
authors.lastname: Kittelson
authors.forename: Karl H
authors.initials: KH
authors.lastname: Pfenninger
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005786:Gene Expression Regulation; D020439:Growth Cones / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D017966:Pyramidal Cells / Q000166:cytology; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D015815:Cell Adhesion Molecules; D007797:Laminin