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Spinal Muscular Atrophy and a Model for Survival of Motor Neuron Protein Function in Axonal Ribonucleoprotein Complexes

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Cell Biology of the Axon

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 48))

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results from loss of function of the SMN1 gene, encoding the ubiquitously expressed survival of motor neuron (SMN) protein, a protein best known for its housekeeping role in the SMN–Gemin multiprotein complex involved in spliceosomal small nuclear ribonucleoprotein (snRNP) assembly. However, numerous studies reveal that SMN has many interaction partners, including mRNA binding proteins and actin regulators, suggesting its diverse role as a molecular chaperone involved in mRNA metabolism. This review focuses on studies suggesting an important role of SMN in regulating the assembly, localization, or stability of axonal messenger ribonucleoprotein (mRNP) complexes. Various animal models for SMA are discussed, and phenotypes described that indicate a predominant function for SMN in neuronal development and synapse formation. These models have begun to be used to test different therapeutic strategies that have the potential to restore SMN function. Further work to elucidate SMN mechanisms within motor neurons and other cell types involved in neuromuscular circuitry hold promise for the potential treatment of SMA.

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Acknowledgment

The authors thank Claudia Fallini, Lei Xing, and Kristy Welshhans for helpful comments. Special thanks to Lei Xing for contributing to Figs. 2 and 3. The authors gratefully acknowledge funding from the Spinal Muscular Atrophy Foundation and NIH (HD055835) to GJB Families of SMS AND NIH (HD056130) to WR.

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    Wilfried Rossoll & Gary J. Bassell

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  1. Wilfried Rossoll
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Rossoll, W., Bassell, G.J. (2009). Spinal Muscular Atrophy and a Model for Survival of Motor Neuron Protein Function in Axonal Ribonucleoprotein Complexes. In: Koenig, E. (eds) Cell Biology of the Axon. Results and Problems in Cell Differentiation, vol 48. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_4

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