This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kiryushko, D.
Right arrow Articles by Bock, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kiryushko, D.
Right arrow Articles by Bock, E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3625-3638, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3625-3638.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Molecular Mechanisms of Ca2+ Signaling in Neurons Induced by the S100A4 Protein

Darya Kiryushko,1,{dagger}* Vera Novitskaya,1,{dagger} Vladislav Soroka,1 Jorg Klingelhofer,2 Eugene Lukanidin,2 Vladimir Berezin,1 and Elisabeth Bock1

Protein Laboratory, Institute of Molecular Pathology, Panum Institute Bld. 6.2, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark,1 Department of Molecular Cancer Biology, Institute of Molecular Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø, Denmark2

Received 17 August 2005/ Returned for modification 13 October 2005/ Accepted 8 February 2006

The S100A4 protein belongs to the S100 family of vertebrate-specific proteins possessing both intra- and extracellular functions. In the nervous system, high levels of S100A4 expression are observed at sites of neurogenesis and lesions, suggesting a role of the protein in neuronal plasticity. Extracellular oligomeric S100A4 is a potent promoter of neurite outgrowth and survival from cultured primary neurons; however, the molecular mechanism of this effect has not been established. Here we demonstrate that oligomeric S100A4 increases the intracellular calcium concentration in primary neurons. We present evidence that both S100A4-induced Ca2+ signaling and neurite extension require activation of a cascade including a heterotrimeric G protein(s), phosphoinositide-specific phospholipase C, and diacylglycerol-lipase, resulting in Ca2+ entry via nonselective cation channels and via T- and L-type voltage-gated Ca2+ channels. We demonstrate that S100A4-induced neurite outgrowth is not mediated by the receptor for advanced glycation end products, a known target for other extracellular S100 proteins. However, S100A4-induced signaling depends on interactions with heparan sulfate proteoglycans at the cell surface. Thus, glycosaminoglycans may act as coreceptors of S100 proteins in neurons. This may provide a mechanism by which S100 proteins could locally regulate neuronal plasticity in connection with brain lesions and neurological disorders.


* Corresponding author. Mailing address: Protein Laboratory, Panum Institute, Blegdamsvej 3C, Bld. 6.2, Copenhagen 2200N, Denmark. Phone: (45) 35 32 73 30. Fax: (45) 35 36 01 16. E-mail: darya{at}plab.ku.dk.

{dagger} D. Kiryushko and V. Novitskaya contributed equally to this work.


Molecular and Cellular Biology, May 2006, p. 3625-3638, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3625-3638.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Hernandez-Ochoa, E. O., Prosser, B. L., Wright, N. T., Contreras, M., Weber, D. J., Schneider, M. F. (2009). Augmentation of Cav1 channel current and action potential duration after uptake of S100A1 in sympathetic ganglion neurons. Am. J. Physiol. Cell Physiol. 297: C955-C970 [Abstract] [Full Text]  
  • Whiteley, A. R., Derome, N., Rogers, S. M., St-Cyr, J., Laroche, J., Labbe, A., Nolte, A., Renaut, S., Jeukens, J., Bernatchez, L. (2008). The Phenomics and Expression Quantitative Trait Locus Mapping of Brain Transcriptomes Regulating Adaptive Divergence in Lake Whitefish Species Pairs (Coregonus sp.). Genetics 180: 147-164 [Abstract] [Full Text]  
  • Cecil, D. L., Terkeltaub, R. (2008). Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes. J. Immunol. 180: 8378-8385 [Abstract] [Full Text]  
  • Kizawa, K., Takahara, H., Troxler, H., Kleinert, P., Mochida, U., Heizmann, C. W. (2008). Specific Citrullination Causes Assembly of a Globular S100A3 Homotetramer: A PUTATIVE Ca2+ MODULATOR MATURES HUMAN HAIR CUTICLE. J. Biol. Chem. 283: 5004-5013 [Abstract] [Full Text]  
  • Leclerc, E., Fritz, G., Weibel, M., Heizmann, C. W., Galichet, A. (2007). S100B and S100A6 Differentially Modulate Cell Survival by Interacting with Distinct RAGE (Receptor for Advanced Glycation End Products) Immunoglobulin Domains. J. Biol. Chem. 282: 31317-31331 [Abstract] [Full Text]  
  • Moretto, M. B., Boff, B., Franco, J., Posser, T., Roessler, T. M., Souza, D. O., Nogueira, C. W., Wofchuk, S., Rocha, J. B. T. (2007). 45Ca2+ Influx in Rat Brain: Effect of Diorganylchalcogenides Compounds. Toxicol Sci 99: 566-571 [Abstract] [Full Text]  
  • Schneider, M., Kostin, S., Strom, C. C., Aplin, M., Lyngbaek, S., Theilade, J., Grigorian, M., Andersen, C. B., Lukanidin, E., Lerche Hansen, J., Sheikh, S. P. (2007). S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes. Cardiovasc Res 75: 40-50 [Abstract] [Full Text]  
  • Sturchler, E., Cox, J. A., Durussel, I., Weibel, M., Heizmann, C. W. (2006). S100A16, a Novel Calcium-binding Protein of the EF-hand Superfamily. J. Biol. Chem. 281: 38905-38917 [Abstract] [Full Text]