OPPOSING FUNCTIONS OF CHONDROITIN SULFATE AND HEPARAN SULFATE DURING EARLY NEURONAL POLARIZATION
OPPOSING FUNCTIONS OF CHONDROITIN SULFATE AND HEPARAN SULFATE DURING EARLY NEURONAL POLARIZATION
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DOI：
10.1016/j.neuroscience.2010.06.027
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发表时间：
2010-09-15
期刊：
影响因子：
3.3
通讯作者：
Maeda, N.
中科院分区：
文献类型：
--
作者：
Nishimura, K.;Ishii, M.;Maeda, N.
神经元的轴突树突极性对于神经系统的信息处理至关重要。在这里，我们使用培养的分离海马神经元研究了硫酸软骨素（CS）和硫酸乙酰肝素（HS）在神经元极化中的功能。对早期培养神经元的免疫组织化学分析表明这些糖胺聚糖的分布有很大不同。虽然 CS 表位积累在轴突和细胞体中存在的焦点接触中，但 HS 的表位在细胞表面（包括树突和轴突）上普遍检测到。用软骨素酶 (CHase) ABC 进行治疗（可降解 CS），并敲低 CS 磺基转移酶 N-乙酰半乳糖胺 4-硫酸 6-O-磺基转移酶 (4,6-ST)（参与过硫酸化结构的生物合成），诱导海马神经元中多个轴突的形成。延时记录显示，经 CHase ABC 处理的神经元的多个轴突高度不稳定，反复延伸和收缩。 CHase ABC 治疗表明，CS 参与磷酸化粘着斑激酶阳性焦点接触的形成。因此，CS 可以增强新生轴突中的整合素信号传导，支持轴突规范。另一方面，当神经元接受特异性降解 HS 的肝素酶处理时，具有单个轴突的神经元增加。 HSase 处理的神经元的轴突稳定延伸，几乎没有收缩。这些结果表明，CS 以相反的方式稳定轴突的生长，而 HS 以相反的方式破坏轴突的生长，从而导致早期神经元极化。 (C) 2010 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Axon-dendrite polarity of neurons is essential for information processing in the nervous system. Here we studied the functions of chondroitin sulfate (CS) and heparan sulfate (HS) in neuronal polarization using cultured dissociated hippocampal neurons. Immunohistochemical analyses of early cultured neurons indicated the distribution of these glycosaminoglycans to be quite different. While CS epitopes were accumulated in the focal contacts present in axons and cell bodies, those of HS were detected ubiquitously on the cell surface including on dendrites and axons. Treatment with chondroitinase (CHase) ABC, which degrades CS, and knockdown of a CS sulfotransferase, N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (4,6-ST), which is involved in the biosynthesis of oversulfated structures, induced the formation of multiple axons in hippocampal neurons. Time-lapse recordings revealed the multiple axons of CHase ABC-treated neurons to be highly unstable, extending and retracting, repeatedly. CHase ABC-treatments suggested that CS is involved in the formation of phosphorylated focal adhesion kinase-positive focal contacts. Thus, CS may enhance integrin signaling in the nascent axons, supporting axon specification. On the other hand, when neurons were treated with heparitinases that specifically degrade HS, neurons with a single axon increased. The axons of HSase-treated neurons extended steadily and showed almost no retraction. These results suggest that CS stabilizes and HS destabilizes the growth of axons in an opposing manner, contributing to early neuronal polarization. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.