Institute for Cell Engineering, The Johns Hopkins University School of Medicine, MD 21205, USA.
Mol Brain. 2008 Oct 15;1:10. doi: 10.1186/1756-6606-1-10.
Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.
几种抑制成熟神经元轴突生长的髓鞘相关因子，包括 Nogo66、髓鞘相关糖蛋白（MAG）和少突胶质细胞髓鞘糖蛋白（OMgp），可以与一种常见的 GPI 连接蛋白 Nogo-66 受体（NgR）结合。越来越多的证据表明，髓鞘抑制剂也通过未知的 NgR 非依赖性机制发出信号。在这里，我们发现 MAG，一种含有 RGD 三肽的蛋白，与β1-整合素形成复合物，介导几种神经元类型的轴突生长锥转向反应。改变 MAG 中 RGD 模体的突变或抑制β1-整合素功能，但不除去 NgR，会消除这些依赖于 MAG 的事件。相比之下，OMgp 诱导的排斥反应不受抑制β1-整合素功能的影响。我们进一步表明，MAG 刺激粘着斑激酶（FAK）的酪氨酸磷酸化，而 FAK 的激活对于 MAG 诱导的生长锥转向是必需的。这些研究确定了β1-整合素是生长锥转向反应中 MAG 的特定介质，通过 FAK 的激活起作用。
