Nano-size motors and meter-long journeys

Neurons have long extensions called axon, which are often more than a meter long. A regulated flow from the cell body provides all the operating materials to the synapses at the end of axons. This process, powered by kinesins, is essential for neuronal homeostasis and brain function. Abnormal axonal transport causes dementia and severe neurodegenerative disorders, such as Amyotrophic Lateral Sclerosis (ALS). Nanometer-size Kinesins and Dyneins function as molecular locomotives within a cell. Advancing 8 nm at each step, they manage all the short and long-range transports within a cell including axonal transport. Our knowledge about these processes has improved in consonance with the technological advances in modern microscopy. Biological systems are driven by weak molecular interactions and local entropy minimization. Activities of individual molecules are also fairly indeterminate. Surprisingly, despite the uncertain nature of individual motor activity, the cellular systems operate in a highly determined fashion. I will discuss how improvements in microscopic techniques have enhanced our understanding of these motors and the axonal transport process, with examples from our laboratory.