Cytoplasmic dynein/dynactin function and dysfunction in motor neurons

The microtubule motor protein cytoplasmic dynein and its activator dynactin are essential in higher eukaryotes, due to critical roles in vesicular transport and cell division. Neurons are uniquely sensitive to defects in dynein/dynactin function, which affect retrograde axonal transport, neurotrophic factor signaling, neurofilament transport, mRNA localization, neuronal migration, and protein recycling and degradation. Mutations in either dynein or dynactin lead to motor neuron degeneration and loss. Recent progress in understanding the cellular mechanisms of dynein/dynactin function, and the effects of dynein/dynactin dysfunction has provided new insight into the roles of microtubule-based motility in the neuron.