HNK-1 (HUMAN NATURAL KILLER-1) GLYCO-EPITOPE IS ESSENTIAL FOR NORMAL SPINE MORPHOGENESIS IN DEVELOPING HIPPOCAMPAL NEURONS
HNK-1 (HUMAN NATURAL KILLER-1) GLYCO-EPITOPE IS ESSENTIAL FOR NORMAL SPINE MORPHOGENESIS IN DEVELOPING HIPPOCAMPAL NEURONS
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DOI：
10.1016/j.neuroscience.2009.09.065
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发表时间：
2009-12-29
期刊：
影响因子：
3.3
通讯作者：
Oka, S.
中科院分区：
文献类型：
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作者：
Morita, I.;Kakuda, S.;Oka, S.
人类自然杀伤剂 1 (HNK-1) 糖表位具有独特的结构特征，即在聚糖非还原末端附着乳糖胺的硫酸化葡萄糖醛酸。 HNK-1 的表达在时间和空间上受到大脑中葡萄糖醛酸转移酶 (GlcAT-P) 的调节。我们之前的报告表明，缺乏 GlcAT-P 的小鼠大脑中几乎完全丧失了 HNK-1 表达，并且海马 CA1 突触的长时程增强 (LTP) 降低。 GlcAT-P 缺陷小鼠还表现出海马依赖性空间学习受损。尽管 HNK-1 在突触可塑性和记忆形成中发挥着重要作用，但 HNK-1 如何调节这些功能仍不清楚。在这项研究中，我们发现HNK-1表位的缺失导致出生后早期小鼠海马和培养的海马神经元中丝状足样未成熟棘的增加和蘑菇样成熟棘的减少。然而，HNK-1 对脊柱密度或丝状足形成没有影响。免疫荧光染色显示，HNK-1的缺失改变了突触后蛋白的分布，例如α-氨基-3-羟基-5-甲基异恶唑丙酸酯（AMPA）型谷氨酸受体亚基GluR2和PSD-95从棘头到树突轴的分布，而不影响突触形成，导致培养的GlcATP缺陷神经元中轴突触的增加。 GluR2 是突触后密度中的主要 HNK-1 载体糖蛋白，具有促进脊柱形态发生的能力。 GluR2的过表达促进了野生型和GlcAT-P缺陷型神经元中脊柱的生长，但GicAT-P缺陷型神经元的增长低于野生型神经元。这是首次证明 HNK-1 是正常树突棘成熟的关键因素，并参与突触后蛋白的分布。 (C) 2009 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
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 GlcATP-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 GicAT-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. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.