[PDF][PDF] Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I

A Kamal, GB Stokin, Z Yang, CH Xia, LSB Goldstein - Neuron, 2000 - cell.com
A Kamal, GB Stokin, Z Yang, CH Xia, LSB Goldstein
Neuron, 2000cell.com
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 K d for binding is 15–20 nM,
with a binding stoichiometry of two APP per KLC. In addition, association of APP with …
Abstract
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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