Subcellular localization and axonal transport of the survival motor neuron(SMN) protein in the developing rat spinal cord

The subcellular localization of the survival motor neuron (SMN) protein, en coded by the spinal muscular atrophy determining gene, was investigated in motor neurons of the developing and adult rat spinal cord by fight and elec tron microscopy immunocytochemistry, The experiments were carried out with a panel of anti-SMN antibodies, all recognizing an SMN-specific protein ban d at 39 kDa in HeLa cells and rat spinal cord protein extracts. SMN protein expression decreased during postnatal spinal cord development, but it rema ined unchanged in distribution and intensity in motor neurons at all ages e xamined. SMN protein was mainly organized in immunoreactive aggregates spar se in the nucleoplasm and cytoplasm of both mature and developing motor neu rons, and it was more rarely localized within the endoplasmic reticulum and in apposition to the external mitochondrial membrane, Most strikingly, the SMN protein was found in association with cytoskeletal elements in spinal dendrites and axons, where it was particularly evident during postnatal dev elopment. The present findings suggest that SMN protein may be transported via axoplasmic flow in maturing neurons. Given the RNA-binding activity of SMN, the SMN protein could be involved in the transport of specific mRNAs i n axons and dendrites of motor neurons. The reduced transport of specific m RNAs within motor neurons during development could play a role in the moton euronal degeneration and impaired axonal sprouting observed in spinal muscu lar atrophy.