Article
- The EMBO Journal (2007) 26, 1475 - 1486
- doi:10.1038/sj.emboj.7601609
Published online: 1 March 2007
Subject Categories:
The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport
Yoichi Araki1, Takanori Kawano1, Hidenori Taru1, Yuhki Saito1, Sachiyo Wada1, Kanako Miyamoto2, Hisako Kobayashi2, Hiroyuki O Ishikawa3, Yu Ohsugi4, Tohru Yamamoto1, Kenji Matsuno2, Masataka Kinjo4 and Toshiharu Suzuki1
- Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
- Department of Biological Science and Technology, Tokyo University of Science, Noda, Japan
- Genome and Drug Research Center, Tokyo University of Science, Noda, Japan
- Laboratory of Supramolecular Biophysics, Research Institute for Electric Science, Hokkaido University, Sapporo, Japan
Correspondence to:
Toshiharu Suzuki, Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita12-Nishi6, Kita-ku, Sapporo 060-0812, Japan. Tel.: +81 11 706 3250; Fax: +81 11 706 4991; E-mail: tsuzuki@pharm.hokudai.ac.jp
Received 22 June 2006; Accepted 24 January 2007
Abstract
Alcadein
(Alc) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alc strongly associates with kinesin light chain (KD
4–8 
10-9 M) through a novel tryptophan- and aspartic acid-containing sequence. Alc can induce kinesin-1 association with vesicles and functions as a novel cargo in axonal anterograde transport. JNK-interacting protein 1 (JIP1), an adaptor protein for kinesin-1, perturbs the transport of Alc, and the kinesin-1 motor complex dissociates from Alc-containing vesicles in a JIP1 concentration-dependent manner. Alc-containing vesicles were transported with a velocity different from that of amyloid 
-protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor. Alc- and APP-containing vesicles comprised mostly separate populations in axons in vivo. Interactions of Alc with kinesin-1 blocked transport of APP-containing vesicles and increased -amyloid generation. Inappropriate interactions of Alc- and APP-containing vesicles with kinesin-1 may promote aberrant APP metabolism in Alzheimer's disease.
Keywords:
- Alcadein,
- Alzheimer's disease,
- APP,
- axonal transport,
- kinesin
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