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Published online on January 29, 2007, 10.1073/pnas.0610660104
PNAS | February 6, 2007 | vol. 104 | no. 6 | 1959-1964


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BIOLOGICAL SCIENCES / NEUROSCIENCE
Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron gene, is specifically involved in axonogenesis

Veronica Setola*, Mineko Terao{dagger}, Denise Locatelli*, Stefania Bassanini*, Enrico Garattini{dagger}, and Giorgio Battaglia*,{ddagger}

*Molecular Neuroanatomy Laboratory, Department of Experimental Neurophysiology and Epileptology, Istituto Neurologico "C. Besta," via Celoria 11, 20133 Milano, Italy; and {dagger}Molecular Biology Laboratory, Centro Catullo e Daniela Borgomainerio, Istituto di Ricerche Farmacologiche "Mario Negri," via Eritrea 62, 20157 Milano, Italy

Communicated by Erminio Costa, University of Illinois, Chicago, IL, December 4, 2006 (received for review December 13, 2005)

Spinal muscular atrophy (SMA) is an autosomal recessive disease of childhood due to loss of the telomeric survival motor neuron gene, SMN1. The general functions of the main SMN1 protein product, full-length SMN (FL-SMN), do not explain the selective motoneuronal loss of SMA. We identified axonal-SMN (a-SMN), an alternatively spliced SMN form, preferentially encoded by the SMN1 gene in humans. The a-SMN transcript and protein are down-regulated during early development in different tissues. In the spinal cord, the a-SMN protein is selectively expressed in motor neurons and mainly localized in axons. Forced expression of a-SMN stimulates motor neuron axonogenesis in a time-dependent fashion and induces axonal-like growth in non-neuronal cells. Exons 2b and 3 are essential for the axonogenic effects. This discovery indicates an unexpected complexity of the SMN gene system and may help in understanding the pathogenesis of SMA.

alternative splicing | neurodegeneration | spinal muscular atrophy | intron retention | axonal sprouting

Author contributions: V.S. and M.T. contributed equally to this work; V.S., M.T., E.G., and G.B. designed research; V.S., M.T., and D.L. performed research; S.B. contributed new reagents/analytic tools; V.S., D.L., and G.B. analyzed data; and E.G. and G.B. wrote the paper.

The authors declare no conflict of interest.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY876898).

{ddagger}To whom correspondence should be addressed. E-mail: battaglia{at}istituto-besta.it

© 2007 by The National Academy of Sciences of the USA


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