Reduced TUBA1A Tubulin Causes Defects in Trafficking and Impaired Adult Motor Behavior
Georgia Buscaglia, Kyle R. Northington, Jeffrey K. Moore, Emily A. Bates
Abstract
Abstract Newly born neurons express high levels of TUBA1A α-tubulin to assemble microtubules for neurite extension and to provide tracks for intracellular transport. In the adult brain, Tuba1a expression decreases dramatically. A mouse that harbors a loss-of-function mutation in the gene encoding TUBA1A ( Tuba1a ND/+ ) allows us to ask whether TUBA1A is important for the function of mature neurons. α-Tubulin levels are about half of wild type in juvenile Tuba1a ND/+ brains, but are close to normal in older animals. In postnatal day (P)0 cultured neurons, reduced TUBA1A allows for assembly of less microtubules in axons resulting in more pausing during organelle trafficking. While Tuba1a ND/+ mouse behavior is indistinguishable from wild-type siblings at weaning, Tuba1a ND/+ mice develop adult-onset ataxia. Neurons important for motor function in Tuba1a ND/+ remain indistinguishable from wild-type with respect to morphology and number and display no evidence of axon degeneration. Tuba1a ND/+ neuromuscular junction (NMJ) synapses are the same size as wild-type before the onset of ataxia, but are reduced in size in older animals. Together, these data indicate that the TUBA1A-rich microtubule tracks that are assembled during development are essential for mature neuron function and maintenance of synapses over time.