Selective motor activation in organelle transport along axons

The active transport of organelles and other cargos along the axon is required to maintain neuronal health and function, but we are just beginning to understand the complex regulatory mechanisms involved. The molecular motors, cytoplasmic dynein and kinesins, transport cargos along microtubules; this transport is tightly regulated by adaptors and effectors. Here we review our current understanding of motor regulation in axonal transport. We discuss the mechanisms by which regulatory proteins induce or repress the activity of dynein or kinesin motors, and explore how this regulation plays out during organelle trafficking in the axon, where motor activity is both cargo specific and dependent on subaxonal location. We survey several well-characterized examples of membranous organelles subject to axonal transport - including autophagosomes, endolysosomes, signalling endosomes, mitochondria and synaptic vesicle precursors - and highlight the specific mechanisms that regulate motor activity to provide localized trafficking within the neuron. Defects in axonal transport have been implicated in conditions ranging from developmental defects in the brain to neurodegenerative disease. Better understanding of the underlying mechanisms will be essential to develop more-effective treatment options. Homeostasis and function of neurons rely on long-distance, bidirectional microtubule-based transport along the axon, which is driven by both dynein and kinesin motors. How these motors are regulated by a plethora of adaptors and effectors to ensure appropriate and robust distribution of cargos is an area of intense study.

Automated summary

The active transport of organelles and other cargos along the axon is essential for maintaining neuronal health and function. However, the complex regulatory mechanisms involved in this process are still not fully understood. This review discusses the current understanding of motor regulation in axonal transport and explores how regulatory proteins affect the activity of dynein or kinesin motors. The specific mechanisms that regulate motor activity during organelle trafficking in the axon are also highlighted.