2-Dependent endocytosis of N-cadherin is regulated by -catenin to facilitate neurite outgrowth
2-Dependent endocytosis of N-cadherin is regulated by -catenin to facilitate neurite outgrowth
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DOI：
10.1111/tra.12473
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发表时间：
2017-05-01
期刊：
影响因子：
4.5
通讯作者：
Tai, Chin-Yin
中科院分区：
文献类型：
--
作者：
Chen, Yi-ting;Tai, Chin-Yin
大脑中回路的形成需要神经突在整个发育过程中生长，以建立与靶细胞的突触接触。几种粘附分子的活性内吞促进这些分子在表面的动态交换，并促进发育中的神经元中的神经突生长。钙依赖性粘附分子N-钙粘蛋白的内吞作用参与了神经突起生长的调控，但其机制尚不清楚。在这里，我们确定了一部分N-钙粘蛋白通过网格蛋白介导的内吞作用（CME）内化。在N-钙粘蛋白的胞质结构域中的两个基于酪氨酸的基序被AP-2接头复合物的2亚基识别，负责N-钙粘蛋白的CME。此外，N-钙粘蛋白粘附复合物的核心成分-连环蛋白通过掩蔽2个基于酪氨酸的基序来抑制N-钙粘蛋白的内吞作用。去除β-连环蛋白有利于2结合N-钙粘蛋白，从而增加网格蛋白介导的N-钙粘蛋白的内吞作用和神经突生长，而不影响表面N-钙粘蛋白的稳态水平。这些结果确定和表征的机制控制N-钙粘蛋白的内吞作用，通过-连环蛋白调节2结合调节神经突生长。
Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N-cadherin, a calcium-dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N-cadherin internalizes through clathrin-mediated endocytosis (CME). Two tyrosine-based motifs in the cytoplasmic domain of N-cadherin recognized by the 2 subunit of the AP-2 adaptor complex are responsible for CME of N-cadherin. Moreover, -catenin, a core component of the N-cadherin adhesion complex, inhibits N-cadherin endocytosis by masking the 2 tyrosine-based motifs. Removal of -catenin facilitates 2 binding to N-cadherin, thereby increasing clathrin-mediated N-cadherin endocytosis and neurite outgrowth without affecting the steady-state level of surface N-cadherin. These results identify and characterize the mechanism controlling N-cadherin endocytosis through -catenin-regulated 2 binding to modulate neurite outgrowth.