The COPI vesicle complex binds and moves with survival motor neuron within axons

Spinal muscular atrophy (SMA), an inherited disease of motor neuron dysfunction, results from insufficient levels of the survival motor neuron (SMN) protein. Movement of the SMN protein as granules within cultured axons suggests that the pathogenesis of SMA may involve defects in neuronal transport, yet the nature of axon transport vesicles remains enigmatic. Here we show that SMN directly binds to the alpha-subunit of the coat protein I (COPI) vesicle coat protein. The alpha-COP protein co-immunoprecipitates with SMN, small nuclear ribonucleoprotein-associated assembly factors and beta-actin mRNA. Although typically Golgi associated, in neuronal cells alpha-COP localizes to lamellipodia and growth cones and moves within the axon, with a subset of these granules traveling together with SMN. Depletion of alpha-COP resulted in mislocalization of SMN and actin at the leading edge at the lamellipodia. We propose that neurons utilize the Golgi-associated COPI vesicle to deliver cargoes necessary for motor neuron integrity and function.