A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems

Giesemann T, Rathke-Hartlieb S, Rothkegel M, Bartsch JW, Buchmeier S, Jockusch BM, Jockusch H (1999)
JOURNAL OF BIOLOGICAL CHEMISTRY 274(53): 37908-37914.

Download
No fulltext has been uploaded. References only!
Journal Article | Original Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ;
Abstract
Spinal muscular atrophy (SMA) is an autosomal, recessive disorder characterized by the loss of a-motoneurons in the spinal cord followed by atrophy of skeletal muscles. SMA-determining candidate genes, SMN1 and SMN2, have been identified on human chromosome 5q. The corresponding SMN protein is expressed ubiquitously. It is coded by seven exons and contains conspicuous proline-rich motifs in its COOH-terminal third (exons 4, 5, and 6). Such motifs are known to bind to profilins (PFNs), small proteins engaged in the control of actin dynamics. We tested whether profilins interact with SMN via its polyproline stretches. Using the yeast two-hybrid system we show that profilins bind to SMN and that this binding depends on its proline-rich motifs, These results were confirmed by coimmunoprecipitation and by in vitro binding studies. Two PFN isoforms, I and II, are known, of which II is characteristic for central nervous system tissue. me show by in situ hybridization that both PFNs are highly expressed in mouse spinal cord and that PFN II is expressed predominantly in neurons. In motoneurons, the primary target of neurodegeneration in SMA, profilins are highly concentrated and colocalize with SMN in the cytoplasm of the cell body and in nuclear gems. Likewise, SMN and PFN I colocalize in gems of HeLa cells. Although SMN interacts with both profilin isoforms, binding of PFN II was stronger than of PFN I in all assays employed. Because the SMN genes are expressed ubiquitously, our findings suggest that the interaction of PFN II with SMN may be involved in neuron-specific effects of SMN mutations.
Publishing Year
ISSN
PUB-ID

Cite this

Giesemann T, Rathke-Hartlieb S, Rothkegel M, et al. A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems. JOURNAL OF BIOLOGICAL CHEMISTRY. 1999;274(53):37908-37914.
Giesemann, T., Rathke-Hartlieb, S., Rothkegel, M., Bartsch, J. W., Buchmeier, S., Jockusch, B. M., & Jockusch, H. (1999). A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems. JOURNAL OF BIOLOGICAL CHEMISTRY, 274(53), 37908-37914. doi:10.1074/jbc.274.53.37908
Giesemann, T., Rathke-Hartlieb, S., Rothkegel, M., Bartsch, J. W., Buchmeier, S., Jockusch, B. M., and Jockusch, H. (1999). A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems. JOURNAL OF BIOLOGICAL CHEMISTRY 274, 37908-37914.
Giesemann, T., et al., 1999. A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems. JOURNAL OF BIOLOGICAL CHEMISTRY, 274(53), p 37908-37914.
T. Giesemann, et al., “A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems”, JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, 1999, pp. 37908-37914.
Giesemann, T., Rathke-Hartlieb, S., Rothkegel, M., Bartsch, J.W., Buchmeier, S., Jockusch, B.M., Jockusch, H.: A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems. JOURNAL OF BIOLOGICAL CHEMISTRY. 274, 37908-37914 (1999).
Giesemann, T, Rathke-Hartlieb, S, Rothkegel, M, Bartsch, JW, Buchmeier, S, Jockusch, BM, and Jockusch, Harald. “A role for polyproline motifs in the spinal muscular atrophy protein SMN - Profilins bind to and colocalize with SMN in nuclear gems”. JOURNAL OF BIOLOGICAL CHEMISTRY 274.53 (1999): 37908-37914.
This data publication is cited in the following publications:
This publication cites the following data publications:

93 Citations in Europe PMC

Data provided by Europe PubMed Central.

BDNF/trkB Induction of Calcium Transients through Cav2.2 Calcium Channels in Motoneurons Corresponds to F-actin Assembly and Growth Cone Formation on β2-Chain Laminin (221).
Dombert B, Balk S, Luningschror P, Moradi M, Sivadasan R, Saal-Bauernschubert L, Jablonka S., Front Mol Neurosci 10(), 2017
PMID: 29163025
Advances in understanding the role of disease-associated proteins in spinal muscular atrophy.
Hosseinibarkooie S, Schneider S, Wirth B., Expert Rev Proteomics 14(7), 2017
PMID: 28635376
Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?
Simone C, Ramirez A, Bucchia M, Rinchetti P, Rideout H, Papadimitriou D, Re DB, Corti S., Cell. Mol. Life Sci. 73(5), 2016
PMID: 26681261
Profilin 1 with the amyotrophic lateral sclerosis associated mutation T109M displays unaltered actin binding and does not affect the actin cytoskeleton.
Freischmidt A, Schopflin M, Feiler MS, Fleck AK, Ludolph AC, Weishaupt JH., BMC Neurosci 16(), 2015
PMID: 26572741
Subcellular localization and Ser-137 phosphorylation regulate tumor-suppressive activity of profilin-1.
Diamond MI, Cai S, Boudreau A, Carey CJ Jr, Lyle N, Pappu RV, Swamidass SJ, Bissell M, Piwnica-Worms H, Shao J., J. Biol. Chem. 290(14), 2015
PMID: 25681442
The SMN structure reveals its crucial role in snRNP assembly.
Seng CO, Magee C, Young PJ, Lorson CL, Allen JP., Hum. Mol. Genet. 24(8), 2015
PMID: 25561692
Molecular evolution of the moonlighting protein SMN in metazoans.
Stump AD, Dillon-White M, Gu S., Comp. Biochem. Physiol. Part D Genomics Proteomics 8(3), 2013
PMID: 23831553
Identification of interaction partners of β-thymosins: application of thymosin β4 labeled by transglutaminase.
App C, Knop J, Mannherz HG, Hannappel E., Ann. N. Y. Acad. Sci. 1270(), 2012
PMID: 23050824
Neurogenic and myogenic contributions to hereditary motor neuron disease.
Bricceno KV, Fischbeck KH, Burnett BG., Neurodegener Dis 9(4), 2012
PMID: 22327341
Structure and functions of profilins.
Krishnan K, Moens PDJ., Biophys Rev 1(2), 2009
PMID: 28509986
Matrix-coated transwell-cultured TM4 sertoli cell testosterone-regulated gene expression mimics in vivo expression.
Prante BC, Garman KL, Sims BN, Lindsey JS., In Vitro Cell. Dev. Biol. Anim. 44(10), 2008
PMID: 18810563
4th UK spinal muscular atrophy (SMA) researchers network meeting.
Parkinson NJ., Neuromuscul. Disord. 18(4), 2008
PMID: 18396402
3rd UK Spinal Muscular Atrophy (SMA) Researchers Network Meeting.
Shaw DJ, Todd AG, Morse R, Young PJ., Neuromuscul. Disord. 17(6), 2007
PMID: 17433679
Post-translational modifications in the survival motor neuron protein.
La Bella V, Kallenbach S, Pettmann B., Biochem. Biophys. Res. Commun. 324(1), 2004
PMID: 15465016

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 10608857
PubMed | Europe PMC

Search this title in

Google Scholar