論文 - 詳細
RRC ID | 71986 |
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著者 | Araki Y, Kawano T, Taru H, Saito Y, Wada S, Miyamoto K, Kobayashi H, Ishikawa HO, Ohsugi Y, Yamamoto T, Matsuno K, Kinjo M, Suzuki T. |
タイトル | The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. |
ジャーナル | EMBO J |
Abstract |
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. |
巻・号 | 26(6) |
ページ | 1475-86 |
公開日 | 2007-3-21 |
DOI | 10.1038/sj.emboj.7601609 |
PII | 7601609 |
PMID | 17332754 |
PMC | PMC1829376 |
MeSH | Adaptor Proteins, Signal Transducing / metabolism Amyloid beta-Protein Precursor / metabolism Animals Axonal Transport / physiology* Blotting, Western Calcium-Binding Proteins / metabolism* Drosophila Immunoprecipitation Kinesins / metabolism* Membrane Proteins / metabolism* Mice Microscopy, Fluorescence Molecular Motor Proteins / metabolism* RNA, Small Interfering / genetics Transport Vesicles / metabolism* Transport Vesicles / physiology |
IF | 9.889 |
リソース情報 | |
遺伝子材料 | KLC1/pcDNA3.1(+) (RDB19590) KLC2/pcDNA3.1(+) (RDB19591) |