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Piazzon, N, Rage, F, Schlotter, F, Moine, H, Branlant, C and Massenet, S (2008) In vitro and in cellulo evidences for association of the survival of motor neuron complex with the fragile X mental retardation protein. J. Biol. Chem. 283:5598-610

Spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein. Although the SMN complex is essential for assembly of spliceosomal U small nuclear RNPs, it is still not understood why reduced levels of the SMN protein specifically cause motor neuron degeneration. SMN was recently proposed to have specific functions in mRNA transport and translation regulation in neuronal processes. The defective protein in Fragile X mental retardation syndrome (FMRP) also plays a role in transport of mRNPs and in their translation. Therefore, we examined possible relationships of SMN with FMRP. We observed granules containing both transiently expressed red fluorescent protein(RFP)-tagged SMN and green fluorescent protein(GFP)-tagged FMRP in cell bodies and processes of rat primary neurons of hypothalamus in culture. By immunoprecipitation experiments, we detected an association of FMRP with the SMN complex in human neuroblastoma SH-SY5Y cells and in murine motor neuron MN-1 cells. Then, by in vitro experiments, we demonstrated that the SMN protein is essential for this association. We showed that the COOH-terminal region of FMRP, as well as the conserved YG box and the region encoded by exon 7 of SMN, are required for the interaction. Our findings suggest a link between the SMN complex and FMRP in neuronal cells.

PubMed Online version:10.1074/jbc.M707304200

Animals; Cell Line, Tumor; Cyclic AMP Response Element-Binding Protein/genetics; Cyclic AMP Response Element-Binding Protein/metabolism; Exons/physiology; Fragile X Mental Retardation Protein/genetics; Fragile X Mental Retardation Protein/metabolism; Fragile X Syndrome/genetics; Fragile X Syndrome/metabolism; Fragile X Syndrome/pathology; Humans; Hypothalamus/metabolism; Hypothalamus/pathology; Mice; Motor Neurons/metabolism; Motor Neurons/pathology; Muscular Atrophy, Spinal/genetics; Muscular Atrophy, Spinal/metabolism; Muscular Atrophy, Spinal/pathology; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Protein Structure, Tertiary/physiology; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; SMN Complex Proteins; Survival of Motor Neuron 1 Protein