Delta-catenin/NPRAP: A new member of the glycogen synthase kinase-3beta signaling complex that promotes beta-catenin turnover in neurons.
Delta-catenin/NPRAP: A new member of the glycogen synthase kinase-3beta signaling complex that promotes beta-catenin turnover in neurons.
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DOI：
10.1002/jnr.22414
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发表时间：
2010-08-15
影响因子：
4.2
通讯作者：
Lu, Qun
中科院分区：
文献类型：
--
作者：
Bareiss, Sonja;Kim, Kwonseop;Lu, Qun
通过多蛋白复合物，糖原合成酶激酶-3 β（GSK-3β）磷酸化并使β-连环蛋白不稳定，β-连环蛋白是神经元生长和适当突触功能的重要信号事件。δ-连环蛋白，或NPRAP（CTNND 2），是β-连环蛋白超家族的神经特异性成员，并且还已知调节神经突生长和突触活性。在这项研究中，我们研究了δ-catenin表达也受GSK-3β信号转导影响的可能性，它参与了调节神经元中β-catenin更新的分子复合物。免疫荧光显微镜显示δ-连环蛋白与分子破坏复合物的成员GSK-3β、β-连环蛋白和APC在大鼠原代神经元中共定位。GSK-3β与δ-catenin形成复合物，其抑制导致δ-catenin和β-catenin表达水平增加。LY 294002和淀粉样蛋白肽（GSK-3β信号传导的已知激活剂）降低δ-连环蛋白表达水平。此外，当用蛋白酶体抑制剂处理神经元时，δ-catenin免疫反应性增加，蛋白质周转减少，这表明δ-catenin的稳定性与β-catenin的稳定性一样，受到蛋白酶体介导的降解的调节。免疫共沉淀实验表明δ-catenin过表达促进GSK-3β和β-catenin的相互作用。用蛋白酶体抑制剂处理的表达δ-catenin的原代皮层神经元和PC 12细胞显示增加的泛素化β-catenin形式。与δ-连环蛋白促进破坏复合物分子相互作用的假设一致，放线菌酮处理过表达δ-连环蛋白的细胞显示出增强的β-连环蛋白更新。这些研究将δ-catenin鉴定为GSK-3β信号通路的新成员，并进一步表明δ-catenin可能参与促进β-catenin在神经元细胞中的相互作用、泛素化和随后的周转。
Through a multiprotein complex, glycogen synthase kinase-3β (GSK-3β) phosphorylates and destabilizes β-catenin, an important signaling event for neuronal growth and proper synaptic function. δ-Catenin, or NPRAP (CTNND2), is a neural specific member of the β-catenin superfamily, and is also known to modulate neurite outgrowth and synaptic activity. In this study, we investigated the possibility that δ-catenin expression is also affected by GSK-3β signaling, and it participates in the molecular complex regulating β-catenin turnover in neurons. Immunofluorescent light microscopy revealed co-localization of δ-catenin with members of the molecular destruction complex: GSK-3β, β-catenin, and APC in rat primary neurons. GSK-3β formed a complex with δ-catenin, and its inhibition resulted in increased δ-catenin and β-catenin expression levels. LY294002 and amyloid peptide, known activators of GSK-3β signaling, reduced δ-catenin expression levels. Furthermore, δ-catenin immunoreactivity increased and protein turnover decreased when neurons were treated with proteasome inhibitors, suggesting that the stability of δ-catenin, like that of β-catenin, is regulated by proteasome-mediated degradation. Co-immunoprecipitation experiments showed that δ-catenin overexpression promoted GSK-3β and β-catenin interactions. Primary cortical neurons and PC12 cells expressing δ-catenin treated with proteasome inhibitors showed increased ubiquitinated β-catenin forms. Consistent with the hypothesis that δ-catenin promotes the interaction of the destruction complex molecules, cycloheximide treatment of cells overexpressing δ-catenin showed enhanced β-catenin turnover. These studies identify δ-catenin as a new member of the GSK-3β signaling pathway and further suggest that δ-catenin is potentially involved in facilitating the interaction, ubiquitination, and subsequent turnover of β-catenin in neuronal cells.
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DOI：
10.1006/bbrc.1999.0364
发表时间：
1999-03-24
影响因子：
3.1
作者：
Ide, N;Hata, Y;Takai, Y
通讯作者：
Takai, Y
影响因子：
--
作者：
Fuentealba, RA;Farias, G;Inestrosa, NC
通讯作者：
Inestrosa, NC
影响因子：
9.2
作者：
Israely, I;Costa, RM;Liu, X
通讯作者：
Liu, X
影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
5.3
作者：
Arikkath, Jyothi;Israely, Inbal;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.