Post-translational modifications in the survival motor neuron protein.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive loss of the spinal motoneurons. The SMA-determining gene has been termed survival motor neuron (SMN) and is deleted or mutated in over 98% of patients. The encoded gene product is a protein expressed as different isoforms. In particular, we showed that the rat SMN cDNA produces two isoforms with M(r) of 32 and 35kDa, both localized in nuclear coiled bodies, but the 32kDa form is also cytoplasmic, whereas the 35kDa form is also microsomal. To determine the molecular relationship between these two isoforms and potential post-translational modifications, we performed transfection experiments with a double-tagged rat SMN. Immunoblot and immunostaining studies demonstrated that the 32kDa SMN isoform derives from the full length 35kDa, through a proteolytic cleavage at the C-terminal. Furthermore, the 35kDa SMN isoform is physiologically phosphorylated in vivo. This may modulate its interaction with molecular partners, either proteins or nucleic acids.
La Bella
Vincenzo
V
Inserm U 382-IBDM, Campus de Luminy, Marseille 13288, France. labella@unipa.it <labella@unipa.it>
Kallenbach
Sacha
S
Pettmann
Brigitte
B
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000166:cytology; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein