不同的 PTPmu 相关信号分子对 E、N 和 R 钙黏蛋白上的神经突生长有不同的调节作用。
Distinct PTPmu-associated signaling molecules differentially regulate neurite outgrowth on E-, N-, and R-cadherin.
机构信息
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
出版信息
Mol Cell Neurosci. 2010 May;44(1):78-93. doi: 10.1016/j.mcn.2010.02.005. Epub 2010 Mar 1.
Classical cadherins play distinct roles in axon growth and guidance in the visual system, however, the signaling pathways they activate remain unclear. Growth cones on each cadherin substrate have a unique morphology suggesting that distinct signals are activated by neurite outgrowth on E-, N-, and R-cadherin. We previously demonstrated that receptor protein tyrosine phosphatase-mu (PTPmu) is required for E- and N-cadherin-dependent neurite outgrowth. In this manuscript, we demonstrate that PTPmu regulates R-cadherin-mediated neurite outgrowth. Furthermore, we evaluated whether known PTPmu-associated signaling proteins, Rac1, Cdc42, IQGAP1 and PKCdelta, regulate neurite outgrowth mediated by these cadherins. While Rac1 activity is required for neurite outgrowth on all three cadherins Cdc42/IQGAP1 are required only for N- and R-cadherin-mediated neurite outgrowth. In addition, we determined that PKC activity is required for E- and R-cadherin-mediated, but not N-cadherin-mediated neurite outgrowth. In summary, distinct PTPmicro-associated signaling proteins are required to promote neurite outgrowth on cadherins.
经典钙黏蛋白在视觉系统的轴突生长和导向中发挥不同的作用,但它们激活的信号通路仍不清楚。每个钙黏蛋白基质上的生长锥具有独特的形态,表明在 E-、N-和 R-钙黏蛋白上的神经突生长激活了不同的信号。我们之前证明了受体蛋白酪氨酸磷酸酶-μ(PTPmu)是 E-和 N-钙黏蛋白依赖性神经突生长所必需的。在本手稿中,我们证明了 PTPmu 调节 R-钙黏蛋白介导的神经突生长。此外,我们评估了已知的 PTPmu 相关信号蛋白 Rac1、Cdc42、IQGAP1 和 PKCδ 是否调节这些钙黏蛋白介导的神经突生长。虽然 Rac1 活性对于三种钙黏蛋白上的神经突生长都是必需的,但 Cdc42/IQGAP1 仅对于 N-和 R-钙黏蛋白介导的神经突生长是必需的。此外,我们确定 PKC 活性对于 E-和 R-钙黏蛋白介导的但不是 N-钙黏蛋白介导的神经突生长是必需的。总之,不同的 PTPmicro 相关信号蛋白是促进钙黏蛋白上神经突生长所必需的。