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The novel cargo Alcadein induces vesicle association of kinesin‐1 motor components and activates axonal transport
Author(s) -
Araki Yoichi,
Kawano Takanori,
Taru Hidenori,
Saito Yuhki,
Wada Sachiyo,
Miyamoto Kanako,
Kobayashi Hisako,
Ishikawa Hiroyuki O,
Ohsugi Yu,
Yamamoto Tohru,
Matsuno Kenji,
Kinjo Masataka,
Suzuki Toshiharu
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601609
Subject(s) - kinesin , vesicle , biology , microbiology and biotechnology , motor protein , vesicular transport protein , molecular motor , axoplasmic transport , synaptic vesicle , microtubule , biochemistry , membrane
Alcadeinα (Alcα) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alcα strongly associates with kinesin light chain ( K D ≈4–8 × 10 −9 M) through a novel tryptophan‐ and aspartic acid‐containing sequence. Alcα 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 Alcα, and the kinesin‐1 motor complex dissociates from Alcα‐containing vesicles in a JIP1 concentration‐dependent manner. Alcα‐containing vesicles were transported with a velocity different from that of amyloid β‐protein precursor (APP)‐containing vesicles, which are transported by the same kinesin‐1 motor. Alcα‐ and APP‐containing vesicles comprised mostly separate populations in axons in vivo . Interactions of Alcα with kinesin‐1 blocked transport of APP‐containing vesicles and increased β‐amyloid generation. Inappropriate interactions of Alc‐ and APP‐containing vesicles with kinesin‐1 may promote aberrant APP metabolism in Alzheimer's disease.