Araki, Y., Kawano, T., Taru, H., Saito, Y., Wada, S., Miyamoto, K., Kobayashi, H., Ishikawa, H.O., Ohsugi, Y., Yamamoto, T., Matsuno, K., Kinjo, M., Suzuki, T. (2007). The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. EMBO J. 26(6): 1475--1486.
FlyBase ID
FBrf0251172
Publication Type
Research paper
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.
