TY - JOUR
T1 - Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron is specifically involved in axonogenesis
AU - Setola, Veronica
AU - Terao, Mineko
AU - Locatelli, Denise
AU - Bassanini, Stefania
AU - Garattiini, Enrico
AU - Battaglia, Giorgio
PY - 2007/2/6
Y1 - 2007/2/6
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Axonal sprouting
KW - Intron retention
KW - Neurodegeneration
KW - Spinal muscular atrophy
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U2 - 10.1073/pnas.0610660104
DO - 10.1073/pnas.0610660104
M3 - Article
C2 - 17261814
AN - SCOPUS:33846930562
VL - 104
SP - 1959
EP - 1964
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6
ER -