First Author | Araki Y | Year | 2007 |
Journal | EMBO J | Volume | 26 |
Issue | 6 | Pages | 1475-86 |
PubMed ID | 17332754 | Mgi Jnum | J:119815 |
Mgi Id | MGI:3703297 | Doi | 10.1038/sj.emboj.7601609 |
Citation | Araki Y, et al. (2007) The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. EMBO J 26(6):1475-86 |
abstractText | 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. |