Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I
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We analyzed the mechanism of axonal transport of the amyloid precursor protein (APP), which plays a major role in the development of Alzheimer's disease. Coimmunoprecipitation, sucrose gradient, and direct in vitro binding demonstrated that APP forms a complex with the microtubule motor, conventional kinesin (kinesin-I), by binding directly to the TPR domain of the kinesin light chain (KLC) subunit. The estimated apparent Kd for binding is 15-20 nM, with a binding stoichiometry of two APP per KLC. In addition, association of APP with microtubules and axonal transport of APP is greatly decreased in a gene-targeted mouse mutant of the neuronally enriched KLC1 gene. We propose that one of the normal functions of APP may be as a membrane cargo receptor for kinesin-I and that KLC is important for kinesin-I-driven transport of APP into axons.
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Characterization of the Kif5B antibodies showed that these antibodies recognize primarily Kif5B (based on in vitro assays with Kif5A and Kif5C) and turned out to be exceptionally clean despite being crude sera.
“Characterization of the Kif5B antibodies showed that these antibodies recognize primarily Kif5B (based on the in vitro assays with Kif5A and Kif5C) and turned out to be exceptionally clean despite being crude sera (38,39).”
From Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides (2008) · cites this paper as [38]
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- Authors
- Kamal, A., Stokin, G. B., Yang, Z., Xia, C.-H., & Goldstein, L. S. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Goldstein, Lawrence S.B
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 28
- Issue
- 2
- Pages
- 449-459
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2056409809
- Cited by
- 544
- References
- 11
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 10 · 2018: 15 · 2017: 9 · 2016: 18 · 2015: 18 · 2014: 26 · 2013: 17 · 2012: 33
- FWCI
- 18.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 35252, R01GM035252)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- amyloid precursor protein, axonal transport, kinesin light chain, KLC1, TPR domain, microtubule motor proteins, protein-protein binding, Alzheimer's disease, axons
- MeSH terms
- Alzheimer Disease, Animals, Epitopes, Axonal Transport, Binding, Competitive, Brain Chemistry, Centrifugation, Density Gradient, Mice, Mutant Strains, Microtubule-Associated Proteins, Microtubules, Precipitin Tests, Recombinant Fusion Proteins, Sciatic Nerve, Blotting, Western, Kinesins, Amyloid beta-Protein Precursor, Protein Structure, Tertiary, Gene Targeting, Mice
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