Subcellular distribution of survival motor neuron (SMN) protein: possible involvement in nucleocytoplasmic and dendritic transport

Spinal muscular atrophy (SMA) is among the most common recessive autosomal diseases and is characterized by the loss of spinal motor neurons. A gene t ermed 'Survival of Motor Neurons' (SMN) has been identified as the SMA-dete rmining gene. Recent work indicates the involvement of the SMN protein and its associated protein SIP1 in spliceosomal snRNP biogenesis. However, the function of SMN remains unknown. Here, we have studied the subcellular loca lization of SMN in the rat spinal cord and more generally in the central ne rvous system (CNS), by light fluorescence and electron microscopy. SMN immu noreactivity (IR) was found in the different regions of the spinal cord but also in various regions of the CNS such as the brainstem, cerebellum, thal amus, cortex and hippocampus. In most neurons, we observed a speckled label ling of the cytoplasm and a discontinuous staining of the nuclear envelope. For some neurons (e.g. brainstem nuclei, dentate gyrus, cortex: layer V) a nd, in particular in motoneurons, SMN-IR was also present as prominent nucl ear dot-like-structures. In these nuclear dots, SMN colocalized with SIP1 a nd with fibrillarin, a marker of coiled bodies. Ultrastructural studies in the anterior horn of the spinal cord confirmed the presence of SMN in the c oiled bodies and also revealed the protein at the external side of nuclear pores complexes, in association with polyribosomes, and in dendrites, assoc iated with microtubules. These localizations suggest that, in addition to i ts involvement in the spliceosome biogenesis, the SMN protein could also pl ay a part in nucleocytoplasmic and dendritic transport.