The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport.
Alcadeinalpha (Alcalpha) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alcalpha strongly associates with kinesin light chain (K(D) approximately 4-8x10(-9) M) through a novel tryptophan- and aspartic acid-containing sequence. Alcalpha 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 Alcalpha, and the kinesin-1 motor complex dissociates from Alcalpha-containing vesicles in a JIP1 concentration-dependent manner. Alcalpha-containing vesicles were transported with a velocity different from that of amyloid beta-protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor. Alcalpha- and APP-containing vesicles comprised mostly separate populations in axons in vivo. Interactions of Alcalpha with kinesin-1 blocked transport of APP-containing vesicles and increased beta-amyloid generation. Inappropriate interactions of Alc- and APP-containing vesicles with kinesin-1 may promote aberrant APP metabolism in Alzheimer's disease.
Araki
Yoichi
Y
Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Kawano
Takanori
T
Taru
Hidenori
H
Saito
Yuhki
Y
Wada
Sachiyo
S
Miyamoto
Kanako
K
Kobayashi
Hisako
H
Ishikawa
Hiroyuki O
HO
Ohsugi
Yu
Y
Yamamoto
Tohru
T
Matsuno
Kenji
K
Kinjo
Masataka
M
Suzuki
Toshiharu
T
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D047468:Immunoprecipitation; D016547:Kinesins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D020409:Molecular Motor Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D022161:Transport Vesicles / Q000378:metabolism* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; C503227:Clstn1 protein, mouse; C490665:Mapk8ip protein, mouse; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D034741:RNA, Small Interfering; D016547:Kinesins