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是一种受体型酪氨酸磷酸酶，使用肝素结合生长因子胸膜蛋白作为配体，并在Morpho中发挥重要作用。在Purkinje细胞中高度表达的Notch受体。酪氨酸基于酪氨酸的排序序列很容易呈抑制作用，但在Andrac内发挥了关键作用。变化变化的变化变化变化变化改变了神经营养的神经营养抑制作用的神经 - 2a细胞的神经突生长的内吞作用，可通过修饰Dner的内部胞内运输来调节Pleiotiotiotiotiotiotiotiotiotiotiotiotiotiotiotiotiotiotion-2a细胞。

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.

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.

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.

Developmental change and function of chondroitin sulfate deposited around Purkinje cells.

浦肯野细胞周围沉积的硫酸软骨素的发育变化和功能。

• 发表时间: 2005
• 期刊: J.Neurosci.Res. 82
• 作者: Shimazaki;Y.;Nagata;I.;Ishii;M.;Tanaka;M.;Marunouchi;T.;Hata;T.;Maeda;N.
• 通讯作者: N.