Author/Editor		Kamal, Adeela; Stokin, Gorazd B; Yang, Zhaohaui; Xia, Chun-Hong; Goldstein, Lawrence SB
Title		Axonal transport of amyloid precursor protein is mediated by direst binding to the kinesin light chain subunit of kinesin-I
Type		članek
Source		Neuron
Vol. and No.		Letnik 28
Publication year		2000
Volume		str. 449-59
Language		eng
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.
Descriptors		ALZHEIMER'S DISEASE AMYLOID BETA-PROTEIN PRECURSOR MICROTUBULE-ASSOCIATED PROTEINS RECOMBINANT FUSION PROTEINS SCIATIC NERVE AXONAL TRANSPORT BINDING, COMPETITIVE BLOTTING, WESTERN BRAIN CHEMISTRY EPITOPES CENTRIFUGATION, DENSITY GRADIENT GENE TARGETING KINESIN MICE, MUTANT STRAINS PRECIPITIN TESTS PROTEIN STRUCTURE, TERTIARY