Abstract
Spinal muscular atrophy (SMA), a common autosomal recessive form of motoneuron disease in infants and young adults, is caused by mutations in the survival motoneuron 1 (SMN1) gene. The corresponding gene product is part of a multiprotein complex involved in the assembly of spliceosomal small nuclear ribonucleoprotein complexes. It is still not understood why reduced levels of the ubiquitously expressed SMN protein specifically cause motoneuron degeneration. Here, we show that motoneurons isolated from an SMA mouse model exhibit normal survival, but reduced axon growth. Overexpression of Smn or its binding partner, heterogeneous nuclear ribonucleoprotein (hnRNP) R, promotes neurite growth in differentiating PC12 cells. Reduced axon growth in Smn-deficient motoneurons correlates with reduced β-actin protein and mRNA staining in distal axons and growth cones. We also show that hnRNP R associates with the 3′ UTR of β-actin mRNA. Together, these data suggest that a complex of Smn with its binding partner hnRNP R interacts with β-actin mRNA and translocates to axons and growth cones of motoneurons.
Bibliography
Rossoll, W., Jablonka, S., Andreassi, C., KroÌning, A.-K., Karle, K., Monani, U. R., & Sendtner, M. (2003). Smn, the spinal muscular atrophyâdetermining gene product, modulates axon growth and localization of β-actin mRNA in growth cones of motoneurons. The Journal of Cell Biology, 163(4), 801â812.
References
49
Referenced
542
10.1523/JNEUROSCI.18-01-00251.1998
/ J. Neurosci. (1998)10.1046/j.1460-9568.1999.00428.x
/ Eur. J. Neurosci. (1999)10.1074/jbc.M006435200
/ J. Biol. Chem. (2001)10.1083/jcb.200212140
/ J. Cell Biol. (2003)10.1083/jcb.200208001
/ J. Cell Biol. (2002)10.1083/jcb.147.4.715
/ J. Cell Biol. (1999)10.1093/hmg/11.12.1439
/ Hum. Mol. Genet. (2002)10.1016/S0300-9084(00)00217-0
/ Biochimie. (2000)10.1093/hmg/11.14.1605
/ Hum. Mol. Genet. (2002)10.1016/S0092-8674(00)80368-2
/ Cell. (1997)10.1093/hmg/9.5.849
/ Hum. Mol. Genet. (2000)10.1016/S0092-8674(00)00102-1
/ Cell. (2000)10.1083/jcb.200105133
/ J. Cell Biol. (2002)10.1038/ng1001-166
/ Nat. Genet. (2001)10.1038/71709
/ Nat. Genet. (2000)10.1093/hmg/9.3.341
/ Hum. Mol. Genet. (2000)10.1093/hmg/10.5.497
/ Hum. Mol. Genet. (2001)10.1083/jcb.123.1.165
/ J. Cell Biol. (1993)10.1083/jcb.127.2.441
/ J. Cell Biol. (1994)10.1083/jcb.136.6.1263
/ J. Cell Biol. (1997)10.1006/bbrc.2001.4679
/ Biochem. Biophys. Res. Commun. (2001)10.1016/0092-8674(95)90460-3
/ Cell. (1995)10.1073/pnas.96.11.6307
/ Proc. Natl. Acad. Sci. USA. (1999)10.1146/annurev.cellbio.18.031802.150501
/ Annu. Rev. Cell Dev. Biol. (2002)10.1038/ng1016
/ Nat. Genet. (2002)10.1083/jcb.200303168
/ J. Cell Biol. (2003)10.1016/S0962-8924(02)02371-1
/ Trends Cell Biol. (2002)10.1016/S1357-2725(01)00047-4
/ Int. J. Biochem. Cell Biol. (2001)10.1093/hmg/8.7.1177
/ Hum. Mol. Genet. (1999)10.1093/hmg/9.3.333
/ Hum. Mol. Genet. (2000)10.1083/jcb.200208079
/ J. Cell Biol. (2003)10.1093/emboj/20.19.5443
/ EMBO J. (2001)10.1093/hmg/9.1.47
/ Hum. Mol. Genet. (2000)10.1016/S0955-0674(02)00332-0
/ Curr. Opin. Cell Biol. (2002)10.1007/s100480050021
/ Neurogenetics. (1997)10.1128/MCB.17.4.2158
/ Mol. Cell. Biol. (1997)10.1093/hmg/11.1.93
/ Hum. Mol. Genet. (2002)10.1038/nn1002
/ Nat. Neurosci. (2003)10.1073/pnas.94.18.9920
/ Proc. Natl. Acad. Sci. USA. (1997)10.1097/00019052-200110000-00012
/ Curr. Opin. Neurol. (2001)10.1242/jcs.114.24.4407
/ J. Cell Sci. (2001)10.1046/j.1460-9568.1999.00585.x
/ Eur. J. Neurosci. (1999)10.1038/83960
/ Nat. Neurosci. (2001)10.1038/ng1001-160
/ Nat. Genet. (2001)10.1083/jcb.141.2.431
/ J. Cell Biol. (1998)10.1006/excr.2000.4858
/ Exp. Cell Res. (2000)10.1083/jcb.147.1.59
/ J. Cell Biol. (1999)10.1016/S0896-6273(01)00357-9
/ Neuron. (2001)10.1523/JNEUROSCI.23-16-06627.2003
/ J. Neurosci. (2003)
Dates
Type | When |
---|---|
Created | 21 years, 9 months ago (Nov. 17, 2003, 8:23 p.m.) |
Deposited | 2 years ago (July 22, 2023, 10:47 a.m.) |
Indexed | 2 weeks, 5 days ago (Aug. 3, 2025, 12:07 a.m.) |
Issued | 21 years, 9 months ago (Nov. 17, 2003) |
Published | 21 years, 9 months ago (Nov. 17, 2003) |
Published Online | 21 years, 9 months ago (Nov. 17, 2003) |
Published Print | 21 years, 8 months ago (Nov. 24, 2003) |
@article{Rossoll_2003, title={Smn, the spinal muscular atrophy–determining gene product, modulates axon growth and localization of β-actin mRNA in growth cones of motoneurons}, volume={163}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200304128}, DOI={10.1083/jcb.200304128}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Rossoll, Wilfried and Jablonka, Sibylle and Andreassi, Catia and Kröning, Ann-Kathrin and Karle, Kathrin and Monani, Umrao R. and Sendtner, Michael}, year={2003}, month=nov, pages={801–812} }