Mice Deficient for the HNK-1 Sulfotransferase Show Alterations in Synaptic Efficacy and Spatial Learning and Memory

Senn, Claudia; Kutsche, Michael; Saghatelyan, Armen; Bösl, Michael R.; Löhler, Jürgen; Bartsch, Udo; Morellini, Fabio; Schachner, Melitta

doi:10.1006/mcne.2002.1142

Cited by 70 publications

(55 citation statements)

References 46 publications

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“…Moreover, TN-R-deficient mutant mice show impaired CA1 LTP, elevated levels of excitatory synaptic transmission, and reduced levels of perisomatic inhibitory currents mediated by γ-aminobutyric acid A (GABA A ) receptors (Bukalo et al 2001;Saghatelyan et al 2001). Several studies suggest that these abnormalities are related to a deficiency in HNK-1 carbohydrate (a structure containing a 3′-sulfated glucuronic acid and first discovered on human natural killer cells; hence the name), which is prominently expressed by TN-R. First, mice deficient in glucuronyltransferase and HNK-1 sulfotransferase, which are the final pathway enzymes in the synthesis of HNK-1 carbohydrate, show a similar reduction in CA1 LTP as that found in TN-R-deficient mice (Senn et al 2002;Yamamoto et al 2002). Second, HNK-1 antibody produces a strong specific reduction in perisomatic inhibitory currents when applied to hippocampal slices (Saghatelyan et al 2000) via relief of the constitutive block of postsynaptic GABA B receptors exerted by endogenous HNK-1 carbohydrate in perisomatic synapses (Fig.…”

Section: Tenascin-r Gabaergic Transmission and Metaplasticitymentioning

confidence: 78%

The extracellular matrix and synapses

2006

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Extracellular matrix (ECM) molecules, derived from both neurons and glial cells, are secreted and accumulate in the extracellular space to regulate various aspects of pre- and postsynaptic differentiation, the maturation of synapses, and their plasticity. The emerging mechanisms comprise interactions of agrin, integrin ligands, and reelin, with their cognate cell-surface receptors being coupled to tyrosine kinase activities. These may induce the clustering of postsynaptic receptors and changes in their composition and function. Furthermore, direct interactions of laminins, neuronal pentraxins, and tenascin-R with voltage-gated Ca(2+) channels, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and gamma-aminobutyric acid(B) (GABA(B)) receptors, respectively, shape the organization and function of different subsets of synapses. Some of these mechanisms significantly contribute to the induction of long-term potentiation in excitatory synapses, either by the regulation of Ca(2+) entry via N-methyl-D-aspartate receptors or L-type Ca(2+) channels, or by the control of GABAergic inhibition.

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Section: Tenascin-r Gabaergic Transmission and Metaplasticitymentioning

confidence: 78%

The extracellular matrix and synapses

2006

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“…CHST10 is known to play an important role in hippocampal plasticity (21), but this is the first report linking its expression to melanoma invasiveness. CHST10, together with two glucuronyltransferases (GlcAT-P and GlcAT-S), directs the biosynthesis of HNK-1 glycan on neural cell adhesion proteins such as NCAM and glycolipids (47).…”

Section: Discussionmentioning

confidence: 91%

“…CHST10 is known to form HNK-1 glycan on neural cell adhesion proteins and glycolipids (18)(19)(20). Expression of the HNK-1 epitope is tightly regulated during embryonic development, when the effects of RA are most critical, and CHST10 plays an important physiologic role in synaptic plasticity of the hippocampus (21). We present evidence that CHST10 suppresses invasiveness but not proliferation in melanoma cells.…”

Section: Introductionmentioning

confidence: 84%

Mechanism of Regulation and Suppression of Melanoma Invasiveness by Novel Retinoic Acid Receptor-γ Target Gene Carbohydrate Sulfotransferase 10

et al. 2009

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Retinoic acid (RA) induces growth arrest and differentiation of S91 murine melanoma cells and serves as a valuable model for this disease. RA acts through activation of RA receptors (RAR), which are members of the nuclear receptor superfamily of ligand-inducible transcription factors. Interestingly, differentiation is mediated by RARγ, but not by RARα or RARβ, suggesting that RARγ possesses unique and uncharacterized molecular properties. To address this question, DNA microarrays in combination with RAR isoform-specific agonists were employed to identify novel RARγ target genes that may play a role in this process. Here, we identified and validated carbohydrate sulfotransferase 10 (CHST10) as a novel RARγ target gene in S91 cells. The RARγ-inducible CHST10 promoter was obtained, and two atypical, independently functioning RA response elements were identified in a 425 bp region. Surprisingly, this fragment is bound by RARγ, but not by RARα or RARβ, thus providing a mechanism for the observed RARγ-specific regulation. CHST10 is a sulfotransferase that forms HNK-1 glycan on neural cell adhesion proteins and glycolipids, and HNK-1 is thought to modulate cell adhesion and possibly metastasis. We show that CHST10 is also regulated by RARγ in a significant subset of human melanoma cells, and three-dimensional cell culture migration assays suggest that CHST10 functions as a suppressor of invasiveness, but not proliferation, in these cells. Induction of CHST10 by RARγ-activating retinoids may present a novel therapeutic strategy to inhibit invasiveness in a subset of melanoma patients. [Cancer Res 2009;69(12):5218-25]

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“…Mice with targeted deletion of the final gene in the HNK-1 synthetic pathway, HNK-1 Sulfotransferase, showed similar defects in LTP. 53 In addition, monoclonal antibodies to HNK-1 also affect LTP in hippocampal slice preparations. 54 Hippocampal changes in schizophrenics have long been reported [55][56][57] and models involving reduced LTP proposed.…”

Section: Discussionmentioning

confidence: 99%

β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation

et al. 2003

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We have mapped and sequenced both chromosome breakpoints of a balanced t(6;11)(q14.2;q25) chromosome translocation that segregates with a schizophrenia-like psychosis. Bioinformatics analysis of the regions revealed a number of confirmed and predicted transcripts. No confirmed transcripts are disrupted by either breakpoint. The chromosome 6 breakpoint region is gene poor, the closest transcript being the serotonin receptor 1E (HTR1E) at 625 kb telomeric to the breakpoint. The chromosome 11 breakpoint is situated close to the telomere. The closest gene, b-1,3-glucuronyltransferase (B3GAT1 or GlcAT-P), is 299 kb centromeric to the breakpoint. B3GAT1 is the key enzyme during the biosynthesis of the carbohydrate epitope HNK-1, which is present on a number of cell adhesion molecules important in neurodevelopment. Mice deleted for the B3GAT1 gene show defects in hippocampal long-term potentiation and in spatial memory formation. We propose that the translocation causes a positional effect on B3GAT1, affecting expression levels and making it a plausible candidate for the psychosis found in this family. More generally, regions close to telomeres are highly polymorphic in both sequence and length in the general population and several studies have implicated subtelomeric deletions as a common cause of idiopathic mental retardation. This leads us to the hypothesis that polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population.

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Mice Deficient for the HNK-1 Sulfotransferase Show Alterations in Synaptic Efficacy and Spatial Learning and Memory

Cited by 70 publications

References 46 publications

The extracellular matrix and synapses

The extracellular matrix and synapses

Mechanism of Regulation and Suppression of Melanoma Invasiveness by Novel Retinoic Acid Receptor-γ Target Gene Carbohydrate Sulfotransferase 10

β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation

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