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Cited by 53Axon Guidance and Neuronal SignalingAlzheimer's disease research and treatmentsCell Adhesion Molecules Research

Amyloid Precursor Protein Is an Autonomous Growth Cone Adhesion Molecule Engaged in Contact Guidance

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Sosa, Lucas J., Bergman, Jared, Estrada-Bernal, Adriana, Glorioso, Thomas J., Kittelson, John M., Pfenninger, Karl H.·2013·PLoS ONE
DOI 10.1371/journal.pone.0064521PMC PMC3653867
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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.

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  • APP-integrin interaction is required for neurite outgrowth and contact guidance.

    “Accordingly, APP–integrin interaction is required for neurite outgrowth and contact guidance [123, 153].”

    From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [123]

    In the Discussion section “Determining APP-Mediated Adhesion” (page unavailable), the paper says APP-mediated adhesion alone can sustain neurite outgrowth and that APP–integrin complexes are not necessary for adhesion; it says their functional role remains unknown. The Results section “APP Influences Axonal Contact Guidance” reports effects of APP expression and integrin knock-down on substrate choice, not a requirement for their interaction. (LLM, conf=0.88)

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  • During development, APP is enriched in axonal growth cones and acts as a co-receptor for guidance cues through its interaction with the extracellular matrix.

    “During development, APP is enriched in axonal growth cones and acts as a co-receptor for guidance cues through its interaction with the extracellular matrix [122, 123].”

    From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [123]

    The Introduction (page unavailable) says APP is enriched in growth cones and binds extracellular-matrix components. It describes an adhesion co-receptor role only as a hypothesis; the Discussion’s Conclusions (page unavailable) instead establish APP as an autonomous adhesion molecule involved in contact guidance. The claim overstates the evidence by saying APP acts as a co-receptor for guidance cues. (LLM, conf=0.88)

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Authors
Sosa, L. J., Bergman, J., Estrada-Bernal, A., Glorioso, T. J., Kittelson, J. M., & Pfenninger, K. H.
Affiliations
  • University of Colorado Anschutz (US)
  • Colorado School of Public Health (US)
Corresponding author
Pfenninger, Karl H.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-05-14
Volume
8
Issue
5
Pages
e64521
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0064521
PMC
PMC3653867
OpenAlex
W2023598911
Cited by
53
References
1
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 2
FWCI
2.42
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Anna and John J. Sie Foundation
  • National Institutes of Health (UL1TR000154, TR000154)
  • National Institute of Neurological Disorders and Stroke (NS061940, R01NS061940)
  • National Center for Advancing Translational Sciences (TR000154)
  • Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Anschutz Medical Campus
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
amyloid precursor protein, contact guidance, adhesion molecules, beta1 integrin, laminin, L1CAM, neurite outgrowth, axon guidance, hippocampal neurons, Alzheimer's disease
MeSH terms
Animals, Axons, Brain, Cell Adhesion, Gene Expression Regulation, Laminin, Cell Adhesion Molecules, Amyloid beta-Protein Precursor, Pyramidal Cells, Growth Cones, Mice, Rats

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