HNK-1 (human natural killer-1) glyco-epitope is essential for normal spine morphogenesis in developing hippocampal neurons.
The human natural killer-1 (HNK-1) glyco-epitope possesses a unique structural feature, a sulfated glucuronic acid attached to lactosamine on the non-reducing termini of glycans. The expression of HNK-1 is temporally and spatially regulated by glucuronyltransferase (GlcAT-P) in the brain. Our previous report showed that mice lacking GlcAT-P almost completely lost HNK-1 expression in the brain and exhibited reduced long-term potentiation (LTP) at hippocampal CA1 synapses. GlcAT-P-deficient mice also showed impaired hippocampus-dependent spatial learning. Although HNK-1 plays an essential role in synaptic plasticity and memory formation, it remains unclear how HNK-1 regulates these functions. In this study, we showed that loss of the HNK-1 epitope resulted in an increase of filopodium-like immature spines and a decrease of mushroom-like mature spines in both the early postnatal mouse hippocampus and cultured hippocampal neurons. However, HNK-1 had no influence on spine density or filopodium formation. Immunofluorescence staining revealed that loss of HNK-1 altered the distribution of postsynaptic proteins such as alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-type glutamate receptor subunit GluR2 and PSD-95 from spine heads onto dendritic shafts without affecting synapse formation, resulting in an increase of shaft synapses in cultured GlcAT-P-deficient neurons. GluR2, a major HNK-1 carrier glycoprotein in postsynaptic density, has the ability to promote spine morphogenesis. Overexpression of GluR2 promoted spine growth in both wild-type and GlcAT-P-deficient neurons, but the increase in GlcAT-P-deficient neurons was lower than that in wild-type neurons. This is the first evidence that HNK-1 is a key factor for normal dendritic spine maturation and is involved in the distribution of postsynaptic proteins.
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
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Morita
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Kakuda
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Y
Takeuchi
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Kawasaki
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Oka
D000818:Animals; D000831:Animals, Newborn; D018959:CD57 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D046508:Culture Techniques; D049229:Dendritic Spines / Q000502:physiology*; D000939:Epitopes; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D055495:Neurogenesis; D017966:Pyramidal Cells / Q000648:ultrastructure*; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology
D018959:CD57 Antigens; D000939:Epitopes; D018091:Receptors, AMPA; D014453:Glucuronosyltransferase; C104722:glutamate receptor ionotropic, AMPA 2