Kinesin molecular motors: Transport pathways, receptors, and human disease

Kinesin molecular motor proteins are responsible for many of the major micr otubule-dependent transport pathways in neuronal and non-neuronal cells. El ucidating the transport pathways mediated by kinesins. the identity of the cargoes moved, and the nature of the proteins that link kinesin motors to c argoes are areas of intense investigation. Kinesin-II recently was found to be required for transport in motile and nonmotile cilia and flagella where it is essential for proper left-right determination in mammalian developme nt, sensory function in ciliated neurons, and opsin transport and viability in photoreceptors. Thus, these pathways and proteins may be prominent cont ributors to several human diseases including ciliary dyskinesias, situs inv ersus, and retinitis pigmentosa. Kinesin-I is needed to move many different types of cargoes in neuronal axons. Two candidates for receptor proteins t hat attach kinesin-I to vesicular cargoes were recently found. One candidat e, sunday driver, is proposed to both link kinesin-I to an unknown vesicula r cargo and to bind and organize the mitogen-activated protein kinase compo nents of a c-Jun N-terminal kinase signaling module. A second candidate, am yloid precursor protein, is proposed to link kinesin-I to a different, also unknown, class of axonal vesicles. The finding of a possible functional in teraction between kinesin-I and amyloid precursor protein may implicate kin esin-I based transport in the development of Alzheimer's disease.