HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 52, 42971-42977, December 30, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/52/42971    most recent M511097200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weinhold, B. Articles by Hildebrandt, H. Search for Related Content PubMed PubMed Citation Articles by Weinhold, B. Articles by Hildebrandt, H. Social Bookmarking                      What's this?

Genetic Ablation of Polysialic Acid Causes Severe Neurodevelopmental Defects Rescued by Deletion of the Neural Cell Adhesion Molecule^*

Birgit Weinhold, Ralph Seidenfaden1, Iris Röckle, Martina Mühlenhoff, Frank Schertzinger, Sidonie Conzelmann, Jamey D. Marth¶, Rita Gerardy-Schahn2, and Herbert Hildebrandt

From the Zelluläre Chemie, Zentrum Biochemie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany, Institut für Zoologie (220), Universität Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany, and ^¶Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093

Poly-2,8-sialic acid (polySia) is a unique modification of the neural cell adhesion molecule, NCAM, tightly associated with neural development and plasticity. However, the vital role attributed to this carbohydrate polymer has been challenged by the mild phenotype of mice lacking polySia due to NCAM-deficiency. To dissect polySia and NCAM functions, we generated polySia-negative but NCAM-positive mice by simultaneous deletion of the two polysialyltransferase genes, St8sia-II and St8sia-IV. Beyond features shared with NCAM-null animals, a severe phenotype with specific brain wiring defects, progressive hydrocephalus, postnatal growth retardation, and precocious death was observed. These drastic defects were selectively rescued by additional deletion of NCAM, demonstrating that they originate from a gain of NCAM functions because of polySia deficiency. The data presented in this study reveal that the essential role of polySia resides in the control and coordination of NCAM interactions during mouse brain development. Moreover, this first demonstration in vivo that a highly specific glycan structure is more important than the glycoconjugate as a whole provides a novel view on the relevance of protein glycosylation for the complex process of building the vertebrate brain.

Received for publication, October 12, 2005

^* This work was supported by grants from the Deutsche Forschungsgemeinschaft (to R. G.-S., H. H., and M. M.), National Institutes of Health (to J. D. M.), the Fonds der Chemischen Industrie (to R. G.-S.), and the Deutsche Krebshilfe (to M. M. and H. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Marseille 9, France.

² To whom correspondence should be addressed. Tel.: 49-511-532-9802; Fax: 49-511-532-8801; E-mail: Gerardy-schahn.rita{at}mh-hannover.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. A. Foley, K. G. Swartzentruber, and K. J. Colley Identification of Sequences in the Polysialyltransferases ST8Sia II and ST8Sia IV That Are Required for the Protein-specific Polysialylation of the Neural Cell Adhesion Molecule, NCAM J. Biol. Chem., June 5, 2009; 284(23): 15505 - 15516. [Abstract] [Full Text] [PDF]

				H. Hildebrandt, M. Muhlenhoff, I. Oltmann-Norden, I. Rockle, H. Burkhardt, B. Weinhold, and R. Gerardy-Schahn Imbalance of neural cell adhesion molecule and polysialyltransferase alleles causes defective brain connectivity Brain, May 14, 2009; (2009) awp117v1. [Abstract] [Full Text] [PDF]

				T. Yoshihara, K. Sugihara, Y. Kizuka, S. Oka, and M. Asano Learning/Memory Impairment and Reduced Expression of the HNK-1 Carbohydrate in {beta}4-Galactosyltransferase-II-deficient Mice J. Biol. Chem., May 1, 2009; 284(18): 12550 - 12561. [Abstract] [Full Text] [PDF]

				Y. Kizuka, Y. Tonoyama, and S. Oka Distinct Transport and Intracellular Activities of Two GlcAT-P Isoforms J. Biol. Chem., April 3, 2009; 284(14): 9247 - 9256. [Abstract] [Full Text] [PDF]

				Y. Kanato, K. Kitajima, and C. Sato Direct binding of polysialic acid to a brain-derived neurotrophic factor depends on the degree of polymerization Glycobiology, December 1, 2008; 18(12): 1044 - 1053. [Abstract] [Full Text] [PDF]

				A. Zelmer, M. Bowen, A. Jokilammi, J. Finne, J. P. Luzio, and P. W. Taylor Differential expression of the polysialyl capsule during blood-to-brain transit of neuropathogenic Escherichia coli K1 Microbiology, August 1, 2008; 154(8): 2522 - 2532. [Abstract] [Full Text] [PDF]

				T. Miyazaki, K. Angata, P. H. Seeberger, O. Hindsgaul, and M. Fukuda CMP substitutions preferentially inhibit polysialic acid synthesis Glycobiology, February 1, 2008; 18(2): 187 - 194. [Abstract] [Full Text] [PDF]

				I. Oltmann-Norden, S. P. Galuska, H. Hildebrandt, R. Geyer, R. Gerardy-Schahn, H. Geyer, and M. Muhlenhoff Impact of the Polysialyltransferases ST8SiaII and ST8SiaIV on Polysialic Acid Synthesis during Postnatal Mouse Brain Development J. Biol. Chem., January 18, 2008; 283(3): 1463 - 1471. [Abstract] [Full Text] [PDF]

				S. P. Galuska, R. Geyer, R. Gerardy-Schahn, M. Muhlenhoff, and H. Geyer Enzyme-dependent Variations in the Polysialylation of the Neural Cell Adhesion Molecule (NCAM) in Vivo J. Biol. Chem., January 4, 2008; 283(1): 17 - 28. [Abstract] [Full Text] [PDF]

				K. Koles, J.-M. Lim, K. Aoki, M. Porterfield, M. Tiemeyer, L. Wells, and V. Panin Identification of N-Glycosylated Proteins from the Central Nervous System of Drosophila Melanogaster Glycobiology, December 1, 2007; 17(12): 1388 - 1403. [Abstract] [Full Text] [PDF]

				T. Glaser, C. Brose, I. Franceschini, K. Hamann, A. Smorodchenko, F. Zipp, M. Dubois-Dalcq, and O. Brustle Neural Cell Adhesion Molecule Polysialylation Enhances the Sensitivity of Embryonic Stem Cell-Derived Neural Precursors to Migration Guidance Cues Stem Cells, December 1, 2007; 25(12): 3016 - 3025. [Abstract] [Full Text] [PDF]

				K. Angata, V. Huckaby, B. Ranscht, A. Terskikh, J. D. Marth, and M. Fukuda Polysialic Acid-Directed Migration and Differentiation of Neural Precursors Are Essential for Mouse Brain Development Mol. Cell. Biol., October 1, 2007; 27(19): 6659 - 6668. [Abstract] [Full Text] [PDF]

				F. Conchonaud, S. Nicolas, M.-C. Amoureux, C. Menager, D. Marguet, P.-F. Lenne, G. Rougon, and V. Matarazzo Polysialylation Increases Lateral Diffusion of Neural Cell Adhesion Molecule in the Cell Membrane J. Biol. Chem., September 7, 2007; 282(36): 26266 - 26274. [Abstract] [Full Text] [PDF]

				S. N. Fewou, H. Ramakrishnan, H. Bussow, V. Gieselmann, and M. Eckhardt Down-regulation of Polysialic Acid Is Required for Efficient Myelin Formation J. Biol. Chem., June 1, 2007; 282(22): 16700 - 16711. [Abstract] [Full Text] [PDF]

				M. A. Lopez-Fernandez, M.-F. Montaron, E. Varea, G. Rougon, C. Venero, D. N. Abrous, and C. Sandi Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation J. Neurosci., April 25, 2007; 27(17): 4552 - 4561. [Abstract] [Full Text] [PDF]

				K. Aoki, M. Perlman, J.-M. Lim, R. Cantu, L. Wells, and M. Tiemeyer Dynamic Developmental Elaboration of N-Linked Glycan Complexity in the Drosophila melanogaster Embryo J. Biol. Chem., March 23, 2007; 282(12): 9127 - 9142. [Abstract] [Full Text] [PDF]

				R. A. Pon, N. J. Biggs, and H. J. Jennings Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor treatment Glycobiology, March 1, 2007; 17(3): 249 - 260. [Abstract] [Full Text] [PDF]

				S. S. Mendiratta, N. Sekulic, F. G. Hernandez-Guzman, B. E. Close, A. Lavie, and K. J. Colley A Novel {alpha}-Helix in the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Is Critical for N-Glycan Polysialylation J. Biol. Chem., November 24, 2006; 281(47): 36052 - 36059. [Abstract] [Full Text] [PDF]

				S. P. Galuska, I. Oltmann-Norden, H. Geyer, B. Weinhold, K. Kuchelmeister, H. Hildebrandt, R. Gerardy-Schahn, R. Geyer, and M. Muhlenhoff Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV J. Biol. Chem., October 20, 2006; 281(42): 31605 - 31615. [Abstract] [Full Text] [PDF]

				O. Senkov, M. Sun, B. Weinhold, R. Gerardy-Schahn, M. Schachner, and A. Dityatev Polysialylated Neural Cell Adhesion Molecule Is Involved in Induction of Long-Term Potentiation and Memory Acquisition and Consolidation in a Fear-Conditioning Paradigm. J. Neurosci., October 18, 2006; 26(42): 10888 - 109898. [Abstract] [Full Text] [PDF]

				W. Zhao, T.-L. L. Chen, B. M. Vertel, and K. J. Colley The CMP-sialic Acid Transporter Is Localized in the Medial-Trans Golgi and Possesses Two Specific Endoplasmic Reticulum Export Motifs in Its Carboxyl-terminal Cytoplasmic Tail J. Biol. Chem., October 13, 2006; 281(41): 31106 - 31118. [Abstract] [Full Text] [PDF]

				T. Avril, S. J. North, S. M. Haslam, H. J. Willison, and P. R. Crocker Probing the cis interactions of the inhibitory receptor Siglec-7 with {alpha}2,8-disialylated ligands on natural killer cells and other leukocytes using glycan-specific antibodies and by analysis of {alpha}2,8-sialyltransferase gene expression J. Leukoc. Biol., October 1, 2006; 80(4): 787 - 796. [Abstract] [Full Text] [PDF]

				P. K. Grewal, M. Boton, K. Ramirez, B. E. Collins, A. Saito, R. S. Green, K. Ohtsubo, D. Chui, and J. D. Marth ST6Gal-I Restrains CD22-Dependent Antigen Receptor Endocytosis and Shp-1 Recruitment in Normal and Pathogenic Immune Signaling. Mol. Cell. Biol., July 1, 2006; 26(13): 4970 - 4981. [Abstract] [Full Text] [PDF]

				C. Florian, J. Foltz, J.-C. Norreel, G. Rougon, and P. Roullet Post-training intrahippocampal injection of synthetic poly-{alpha}-2,8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice Learn. Mem., May 1, 2006; 13(3): 335 - 341. [Abstract] [Full Text] [PDF]