Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I.
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.
Mesh Terms:
Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Axonal Transport, Binding, Competitive, Blotting, Western, Brain Chemistry, Centrifugation, Density Gradient, Epitopes, Gene Targeting, Kinesin, Mice, Mice, Mutant Strains, Microtubule-Associated Proteins, Microtubules, Precipitin Tests, Protein Structure, Tertiary, Recombinant Fusion Proteins, Sciatic Nerve
Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Axonal Transport, Binding, Competitive, Blotting, Western, Brain Chemistry, Centrifugation, Density Gradient, Epitopes, Gene Targeting, Kinesin, Mice, Mice, Mutant Strains, Microtubule-Associated Proteins, Microtubules, Precipitin Tests, Protein Structure, Tertiary, Recombinant Fusion Proteins, Sciatic Nerve
Neuron
Date: Nov. 01, 2000
PubMed ID: 11144355
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