Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of {beta}-actin mRNA in growth cones of motoneurons

doi:10.1083/jcb.200304128

Published online 17 November 2003. doi:10.1083/jcb.200304128

This Article

	Full Text
	Full Text (PDF, 641K)
	PPT slides of all figures
	Supplemental Material Index
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Rossoll, W.
	Articles by Sendtner, M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Rossoll, W.
	Articles by Sendtner, M.


Related Collections

	Related Article

Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2003/11/801 $8.00
The Journal of Cell Biology, Volume 163, Number 4, 801-812

Article

Smn, the spinal muscular atrophy–determining gene product, modulates axon growth and localization of ß-actin mRNA in growth cones of motoneurons

Wilfried Rossoll¹, Sibylle Jablonka¹, Catia Andreassi¹, Ann-Kathrin Kröning¹, Kathrin Karle¹, Umrao R. Monani² and Michael Sendtner¹

¹ Institute for Clinical Neurobiology, University of Wuerzburg, 97080 Wuerzburg, Germany
² Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210

Address correspondence to Michael Sendtner, Institute for Clinical Neurobiology, Josef-Schneider-Str. 11, 97080 Wuerzburg, Germany. Tel.: (49) 931-201-49767. Fax: (49) 931-201-49788. email: sendtner{at}mail.uni-wuerzburg.de

Spinal muscular atrophy (SMA), a common autosomal recessiveform of motoneuron disease in infants and young adults, is causedby mutations in the survival motoneuron 1 (SMN1) gene. The correspondinggene product is part of a multiprotein complex involved in theassembly of spliceosomal small nuclear ribonucleoprotein complexes.It is still not understood why reduced levels of the ubiquitouslyexpressed SMN protein specifically cause motoneuron degeneration.Here, we show that motoneurons isolated from an SMA mouse modelexhibit normal survival, but reduced axon growth. Overexpressionof Smn or its binding partner, heterogeneous nuclear ribonucleoprotein(hnRNP) R, promotes neurite growth in differentiating PC12 cells.Reduced axon growth in Smn-deficient motoneurons correlateswith reduced ß-actin protein and mRNA staining indistal axons and growth cones. We also show that hnRNP R associateswith the 3' UTR of ß-actin mRNA. Together, these datasuggest that a complex of Smn with its binding partner hnRNPR interacts with ß-actin mRNA and translocates toaxons and growth cones of motoneurons.

Key Words: SMA; SMN; RNA transport; ß-actin; hnRNP R

W. Rossoll and S. Jablonka contributed equally to this paper.

The online version of this article includes supplemental material.

Abbreviations used in this paper: hnRNP, heterogeneous nuclearribonucleoprotein; phospho-tau, phosphorylated tau protein;RRM, RNA recognition motif; SMA, spinal muscular atrophy; SMN,survival motoneuron; snRNPs, small nuclear ribonucleoproteins.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

Related Article

A disease of actin transport?: William A. Wells
J. Cell Biol. 2003 163: 689. [Full Text] [PDF]

This article has been cited by other articles:

Kundel, M., Jones, K. J., Shin, C. Y., Wells, D. G. (2009). Cytoplasmic Polyadenylation Element-Binding Protein Regulates Neurotrophin-3-Dependent {beta}-Catenin mRNA Translation in Developing Hippocampal Neurons. J. Neurosci. 29: 13630-13639 [Abstract] [Full Text]
Mattis, V. B., Ebert, A. D., Fosso, M. Y., Chang, C.-W., Lorson, C. L. (2009). Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model. Hum Mol Genet 18: 3906-3913 [Abstract] [Full Text]
Garbes, L., Riessland, M., Holker, I., Heller, R., Hauke, J., Trankle, C., Coras, R., Blumcke, I., Hahnen, E., Wirth, B. (2009). LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate. Hum Mol Genet 18: 3645-3658 [Abstract] [Full Text]
Boon, K.-L., Xiao, S., McWhorter, M. L., Donn, T., Wolf-Saxon, E., Bohnsack, M. T., Moens, C. B., Beattie, C. E. (2009). Zebrafish survival motor neuron mutants exhibit presynaptic neuromuscular junction defects. Hum Mol Genet 18: 3615-3625 [Abstract] [Full Text]
Workman, E., Saieva, L., Carrel, T. L., Crawford, T. O., Liu, D., Lutz, C., Beattie, C. E., Pellizzoni, L., Burghes, A. H.M. (2009). A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Hum Mol Genet 18: 2215-2229 [Abstract] [Full Text]
Guenther, U.-P., Handoko, L., Laggerbauer, B., Jablonka, S., Chari, A., Alzheimer, M., Ohmer, J., Plottner, O., Gehring, N., Sickmann, A., von Au, K., Schuelke, M., Fischer, U. (2009). IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1). Hum Mol Genet 18: 1288-1300 [Abstract] [Full Text]
Kong, L., Wang, X., Choe, D. W., Polley, M., Burnett, B. G., Bosch-Marce, M., Griffin, J. W., Rich, M. M., Sumner, C. J. (2009). Impaired Synaptic Vesicle Release and Immaturity of Neuromuscular Junctions in Spinal Muscular Atrophy Mice. J. Neurosci. 29: 842-851 [Abstract] [Full Text]
Chen, H.-H., Chang, J.-G., Lu, R.-M., Peng, T.-Y., Tarn, W.-Y. (2008). The RNA Binding Protein hnRNP Q Modulates the Utilization of Exon 7 in the Survival Motor Neuron 2 (SMN2) Gene. Mol. Cell. Biol. 28: 6929-6938 [Abstract] [Full Text]
Walker, M. P., Rajendra, T.K., Saieva, L., Fuentes, J. L., Pellizzoni, L., Matera, A. G. (2008). SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet 17: 3399-3410 [Abstract] [Full Text]
McGovern, V. L., Gavrilina, T. O., Beattie, C. E., Burghes, A. H.M. (2008). Embryonic motor axon development in the severe SMA mouse. Hum Mol Genet 17: 2900-2909 [Abstract] [Full Text]
Oprea, G. E., Krober, S., McWhorter, M. L., Rossoll, W., Muller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B. (2008). Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy. Science 320: 524-527 [Abstract] [Full Text]
Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H.M. (2008). Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect. Hum Mol Genet 17: 1063-1075 [Abstract] [Full Text]
Murray, L. M., Comley, L. H., Thomson, D., Parkinson, N., Talbot, K., Gillingwater, T. H. (2008). Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet 17: 949-962 [Abstract] [Full Text]
Ratti, A., Fallini, C., Colombrita, C., Pascale, A., Laforenza, U., Quattrone, A., Silani, V. (2008). Post-transcriptional Regulation of Neuro-oncological Ventral Antigen 1 by the Neuronal RNA-binding Proteins ELAV. J. Biol. Chem. 283: 7531-7541 [Abstract] [Full Text]
Piazzon, N., Rage, F., Schlotter, F., Moine, H., Branlant, C., Massenet, S. (2008). In Vitro and in Cellulo Evidences for Association of the Survival of Motor Neuron Complex with the Fragile X Mental Retardation Protein. J. Biol. Chem. 283: 5598-5610 [Abstract] [Full Text]
Tadesse, H., Deschenes-Furry, J., Boisvenue, S., Cote, J. (2008). KH-type splicing regulatory protein interacts with survival motor neuron protein and is misregulated in spinal muscular atrophy. Hum Mol Genet 17: 506-524 [Abstract] [Full Text]
Barrandon, C., Bonnet, F., Nguyen, V. T., Labas, V., Bensaude, O. (2007). The Transcription-Dependent Dissociation of P-TEFb-HEXIM1-7SK RNA Relies upon Formation of hnRNP-7SK RNA Complexes. Mol. Cell. Biol. 27: 6996-7006 [Abstract] [Full Text]
Jablonka, S., Beck, M., Lechner, B. D., Mayer, C., Sendtner, M. (2007). Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy. JCB 179: 139-149 [Abstract] [Full Text]
Morse, R., Shaw, D. J., Todd, A. G., Young, P. J. (2007). Targeting of SMN to Cajal bodies is mediated by self-association. Hum Mol Genet 16: 2349-2358 [Abstract] [Full Text]
Vitte, J., Fassier, C., Tiziano, F. D., Dalard, C., Soave, S., Roblot, N., Brahe, C., Saugier-Veber, P., Bonnefont, J. P., Melki, J. (2007). Refined Characterization of the Expression and Stability of the SMN Gene Products. Am. J. Pathol. 171: 1269-1280 [Abstract] [Full Text]
Sumner, C. J. (2007). Molecular Mechanisms of Spinal Muscular Atrophy. J Child Neurol 22: 979-989 [Abstract]
Kolb, S. J., Battle, D. J., Dreyfuss, G. (2007). Molecular Functions of the SMN Complex. J Child Neurol 22: 990-994 [Abstract]
Beattie, C. E., Carrel, T. L., McWhorter, M. L. (2007). Fishing for a Mechanism: Using Zebrafish to Understand Spinal Muscular Atrophy. J Child Neurol 22: 995-1003 [Abstract]
Schmid, A., DiDonato, C. J. (2007). Animal Models of Spinal Muscular Atrophy. J Child Neurol 22: 1004-1012 [Abstract]
van Bergeijk, J., Rydel-Konecke, K., Grothe, C., Claus, P. (2007). The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus. FASEB J. 21: 1492-1502 [Abstract] [Full Text]
Rajendra, T.K., Gonsalvez, G. B., Walker, M. P., Shpargel, K. B., Salz, H. K., Matera, A. G. (2007). A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. JCB 176: 831-841 [Abstract] [Full Text]
Ting, C.-H., Lin, C.-W., Wen, S.-L., Hsieh-Li, H.-M., Li, H. (2007). Stat5 constitutive activation rescues defects in spinal muscular atrophy. Hum Mol Genet 16: 499-514 [Abstract] [Full Text]
Setola, V., Terao, M., Locatelli, D., Bassanini, S., Garattini, E., Battaglia, G. (2007). Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron gene, is specifically involved in axonogenesis. Proc. Natl. Acad. Sci. USA 104: 1959-1964 [Abstract] [Full Text]
Carrel, T. L., McWhorter, M. L., Workman, E., Zhang, H., Wolstencroft, E. C., Lorson, C., Bassell, G. J., Burghes, A. H. M., Beattie, C. E. (2006). Survival Motor Neuron Function in Motor Axons Is Independent of Functions Required for Small Nuclear Ribonucleoprotein Biogenesis. J. Neurosci. 26: 11014-11022 [Abstract] [Full Text]
Zhang, H., Xing, L., Rossoll, W., Wichterle, H., Singer, R. H., Bassell, G. J. (2006). Multiprotein Complexes of the Survival of Motor Neuron Protein SMN with Gemins Traffic to Neuronal Processes and Growth Cones of Motor Neurons.. J. Neurosci. 26: 8622-8632 [Abstract] [Full Text]
Sumner, C. J., Kolb, S. J., Harmison, G. G., Jeffries, N. O., Schadt, K., Finkel, R. S., Dreyfuss, G., Fischbeck, K. H. (2006). SMN mRNA and protein levels in peripheral blood: Biomarkers for SMA clinical trials. Neurology 66: 1067-1073 [Abstract] [Full Text]
Renvoise, B., Khoobarry, K., Gendron, M.-C., Cibert, C., Viollet, L., Lefebvre, S. (2006). Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells. J. Cell Sci. 119: 680-692 [Abstract] [Full Text]
Jablonka, S., Karle, K., Sandner, B., Andreassi, C., von Au, K., Sendtner, M. (2006). Distinct and overlapping alterations in motor and sensory neurons in a mouse model of spinal muscular atrophy. Hum Mol Genet 15: 511-518 [Abstract] [Full Text]
Gabanella, F., Carissimi, C., Usiello, A., Pellizzoni, L. (2005). The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Hum Mol Genet 14: 3629-3642 [Abstract] [Full Text]
Gallo, J.-M., Jin, P., Thornton, C. A., Lin, H., Robertson, J., D'Souza, I., Schlaepfer, W. W. (2005). The Role of RNA and RNA Processing in Neurodegeneration. J. Neurosci. 25: 10372-10375 [Full Text]
Winkler, C., Eggert, C., Gradl, D., Meister, G., Giegerich, M., Wedlich, D., Laggerbauer, B., Fischer, U. (2005). Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Genes Dev. 19: 2320-2330 [Abstract] [Full Text]
Jarecki, J., Chen, X., Bernardino, A., Coovert, D. D., Whitney, M., Burghes, A., Stack, J., Pollok, B. A. (2005). Diverse small-molecule modulators of SMN expression found by high-throughput compound screening: early leads towards a therapeutic for spinal muscular atrophy. Hum Mol Genet 14: 2003-2018 [Abstract] [Full Text]
Kernochan, L. E., Russo, M. L., Woodling, N. S., Huynh, T. N., Avila, A. M., Fischbeck, K. H., Sumner, C. J. (2005). The role of histone acetylation in SMN gene expression. Hum Mol Genet 14: 1171-1182 [Abstract] [Full Text]
Wolstencroft, E. C., Mattis, V., Bajer, A. A., Young, P. J., Lorson, C. L. (2005). A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels. Hum Mol Genet 14: 1199-1210 [Abstract] [Full Text]
Gangwani, L., Flavell, R. A., Davis, R. J. (2005). ZPR1 Is Essential for Survival and Is Required for Localization of the Survival Motor Neurons (SMN) Protein to Cajal Bodies. Mol. Cell. Biol. 25: 2744-2756 [Abstract] [Full Text]
Vitte, J. M., Davoult, B., Roblot, N., Mayer, M., Joshi, V., Courageot, S., Tronche, F., Vadrot, J., Moreau, M. H., Kemeny, F., Melki, J. (2004). Deletion of Murine Smn Exon 7 Directed to Liver Leads to Severe Defect of Liver Development Associated with Iron Overload. Am. J. Pathol. 165: 1731-1741 [Abstract] [Full Text]
Grohmann, K., Rossoll, W., Kobsar, I., Holtmann, B., Jablonka, S., Wessig, C., Stoltenburg-Didinger, G., Fischer, U., Hubner, C., Martini, R., Sendtner, M. (2004). Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1). Hum Mol Genet 13: 2031-2042 [Abstract] [Full Text]
Chittka, A., Arevalo, J. C., Rodriguez-Guzman, M., Perez, P., Chao, M. V., Sendtner, M. (2004). The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E. JCB 164: 985-996 [Abstract] [Full Text]