Cargo-carrying motor vehicles on the neuronal highway: transport pathways and neurodegenerative disease.
Within axons vital cargoes must be transported over great distances along microtubule tracks to maintain neuronal viability. Essential to this system are the molecular motors, kinesin and dynein, which transport a variety of neuronal cargoes. Elucidating the transport pathways, the identity of the cargoes transported, and the regulation of motor-cargo complexes are areas of intense investigation. Evidence suggests that essential components, including signaling proteins, neuroprotective and repair molecules, and vesicular and cytoskeletal components are all transported. In addition newly emerging data indicate that defects in axonal transport pathways may contribute to the initiation or progression of chronic neuronal dysfunction. In this review we concentrate on microtubule-based motor proteins, their linkers, and cargoes and discuss how factors in the axonal transport pathway contribute to disease states. As additional cargo complexes and transport pathways are identified, an understanding of the role these pathways play in the development of human disease will hopefully lead to new diagnostic and treatment strategies.
Gunawardena
Shermali
S
Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, California 92093-0683, USA.
Goldstein
Lawrence S B
LS
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D003411:Arvicolinae / Q000378:metabolism; D001692:Biological Transport; D036022:Capsid Proteins / Q000378:metabolism; D002352:Carrier Proteins; D004198:Disease Susceptibility; D006801:Humans; D020409:Molecular Motor Proteins / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology
D033942:Adaptor Proteins, Vesicular Transport; D036022:Capsid Proteins; D002352:Carrier Proteins; D020409:Molecular Motor Proteins; D021382:Protein Sorting Signals