HETEROGENEITY OF SUBCELLULAR-LOCALIZATION AND ELECTROPHORETIC MOBILITY OF SURVIVAL MOTOR-NEURON (SMN) PROTEIN IN MAMMALIAN NEURAL CELLS ANDTISSUES

Spinal muscular atrophy is caused by defects in the survival motor neu ron (SMN) gene. To better understand the patterns of expression of SMN in neuronal cells and tissues, we raised a polyclonal antibody (abSMN ) against a synthetic oligopeptide from SMN exon 2. AbSMN immunostaini ng in neuroblastoma cells and mouse and human central nervous system ( CNS) showed intense labeling of nuclear ''gems,'' along with prominent nucleolar immunoreactivity in mouse and human CNS tissues. Strong cyt oplasmic labeling was observed in the perikarya and proximal dendrites of human spinal motor neurons but not in their axons, Immunoblot anal ysis revealed a 34-kDa species in the insoluble protein fractions from human SY5Y neuroblastoma cells, embryonic mouse spinal cord cultures, and human CNS tissue. By contrast, a 38-kDa species was detected in t he cytosolic fraction of SY5Y cells, We conclude that SMN protein is e xpressed prominently in both the cytoplasm and nucleus in multiple typ es of neurons in brain and spinal cord, a finding consistent with a ro le for SMN as a determinant of neuronal viability.