Abstract
Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.
Original language | English (US) |
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Pages (from-to) | 2657-2667 |
Number of pages | 11 |
Journal | Journal of Neuroscience Research |
Volume | 85 |
Issue number | 12 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- Motor neuron disease
- Ribonucleoprotein (RNP)
- Spinal muscular atrophy (SMA)
- Survival of motor neuron protein (SMN)
- mRNA localization
- mRNA transport
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience