Signal transduction of chondroitin sulfate proteoglycans and neuronal network formation

硫酸软骨素蛋白聚糖的信号转导和神经元网络形成

• 批准号: 17500268
• 负责人: MAEDA Nobuaki
• 金额: $ 2.24万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500268/
• 关键词: Chondroitin sulfate; Proteoglycan; Cerebellum; Pleiotrophin; Tyrosine phosphorylation; プレイオトロフィン; ホスファカン; チロシン燐酸化; PTPζ

PTPζ, a receptor-type protein tyrosine phosphatase, uses a heparin-binding growth factor pleiotrophin as a ligand and play important roles in the morphogenesis of cerebellar Purkinje cells. In this study, we studied functional interaction between PTPζ and DNER, a Delta/Notch-like receptor highly expressed in Purkinje cells. PTPζ and DNER displayed patchy co-localization in the dendritic shafts of Purkinje cells and in the COS-7 transfectants expressing both proteins. Immunoprecipitation experiments indicated that PTPζ and DNER formed complex both in vivo and in vitro. Several tyrosine residues in the intracellular region of DNER including the ones in and adjacent to the tyrosine-based sorting motif were phosphorylated, and were easily dephosphorylated by the PTPζ catalytic domain. The tyrosine-based sorting motif played critical roles in the endocytosis and intracellular transport of DNER, and tyrosine phosphorylation and destruction of this motif resulted in the accumulation of DNER on the plasma membrane of the PTPζ-expressing cells. Accumulation of DNER on the plasma membrane of Neuro-2A cells led to the morphological changes including extension of processes. Pleiotrophin suppressed the endocytosis of DNER and DNER-induced inhibition of neurite outgrowth of Neuro-2A cells. These observations suggests that pleiotrophin-PTPζ signaling regulates the morphogenesis of Purkinje cells by modifying the intracellular transport of DNER.

PTPζ是一种受体型蛋白酪氨酸磷酸酶，使用肝素结合生长因子多叶酸蛋白作为配体，并在小脑普林吉细胞的形态发生中起重要作用。在这项研究中，我们研究了PTPζ和DNER之间的功能相互作用，Dner是一种在Purkinje细胞中高度表达的Delta/Notch样受体。 PTPζ和DNER在Purkinje细胞的树突轴以及表达这两种蛋白的Cos-7转染剂中显示出斑驳的共定位。免疫沉淀实验表明，PTPζ和DNER在体内和体外都形成复合物。几种酪氨酸保留在DNER的细胞内区域中，其中包括基于酪氨酸的排序基序中的酪氨酸和邻近的酪氨酸被磷酸化，并且很容易被PTPζ催化结构域脱磷酸化。基于酪氨酸的分选基序在DNER的内吞和细胞内转运中起着关键作用，该基序的酪氨酸磷酸化和破坏导致DNER在表达PTPζ细胞的质膜上积累。 DNER在神经2a细胞的质膜上的积累导致形态学变化，包括延伸过程。多叶酸抑制了DNER的内吞作用，并抑制了DNER诱导的神经2A细胞神经过结的抑制作用。这些观察结果表明，多叶蛋白-ptpζ信号通过修饰DNER的细胞内转运来调节Purkinje细胞的形态发生。

项目成果

Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain.

• DOI: 10.1093/glycob/cwi090
• 发表时间: 2005-10
• 期刊: Glycobiology
• 影响因子: 4.3
• 作者: T. Yabe;T. Hata;Jue He;N. Maeda

A chondroitin sulfate proteoglycan, PTPζ/phosphacan, and neuronal network formation.

硫酸软骨素蛋白多糖、PTP z/磷酸聚糖和神经元网络形成。

• 期刊: Neuronal Network Research Horizons(Martin L.Weiss(ed))(Nova Science, USA) (In press)
• 作者: Maeda;N.;et al.
• 通讯作者: et al.

PTPζ/phosphacan : Multifunctional receptor-type chondroitin sulfate proteoglycan.

PTPδ/磷酸聚糖：多功能受体型硫酸软骨素蛋白多糖。

• 期刊: Neural Proteoglycans(Maeda, N.(ed))(Research Signpost, India) (In press)
• 作者: Maeda;N.;et al.
• 通讯作者: et al.

Chondroitin sulfate proteoglycans and neuronal network formation.

硫酸软骨素蛋白聚糖和神经元网络形成。

• 期刊: Glycoscience Lab Manual(Taniguchi, N.(ed))(Springer Japan) (In press)
• 作者: Maeda;N.;et al.
• 通讯作者: et al.

未来を拓く糖鎖科学(永井克孝編)

开辟未来的糖科学（永井胜隆编辑）

• 发表时间: 2005
• 作者: Maeda;N.;et al.;MAEDA Nobuaki;MAEDA Nobuaki;MAEDA Nobuaki;前田信明
• 通讯作者: 前田信明