RRC ID 71986
Author 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.
Title The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport.
Journal 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.
Volume 26(6)
Pages 1475-86
Published 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
DNA material KLC1/pcDNA3.1(+) (RDB19590) KLC2/pcDNA3.1(+) (RDB19591)