Expression of the survival of motor neuron (SMN) gene in primary neurons and increase in SMN levels by activation of the N-methyl-D-aspartate glutamate receptor.
Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease caused by mutations of the survival of motor neuron (SMN) gene. The SMN protein is expressed ubiquitously as part of a 300-kilodalton multi-protein complex, incorporating several proteins critically required in pre-mRNA splicing. Although SMN mutations render SMN defective in this role, the specific alpha-motor neuron degenerative phenotype seen in the disease remains unexplained. During the differentiation process of spinal motor neurons and cerebellar granule cells, the acquisition of mature electrophysiological and molecular properties is linked to the activation of the glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. We have used primary cultures of rat cerebellar granules to study SMN expression during neuronal differentiation in vitro and in response to the activation of the NMDA receptor. We report that the expression of gems, the nuclear structures where SMN concentrates, is developmentally regulated. The highest expression is associated with the cell clustering phase and expression of NMDA receptors. Stimulation of the NMDA receptor induces an increase in gem number and in SMN transcription, through activation of its promoter. These results demonstrate that SMN levels are dependent on synaptic activity, implying that SMN may have important neuron-specific functions downstream of synaptic activation.
Andreassi
Catia
C
Institute of General Pathology, Universita' Cattolica del Sacro Cuore, Rome, Italy.
Patrizi
Anna Letizia
AL
Monani
Umrao R
UR
Burghes
A H M
AH
Brahe
Christina
C
Eboli
Maria Luisa
ML
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D017362:Cyclic AMP Response Element-Binding Protein; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D016202:N-Methylaspartate