Yamashita Naoya, Uchida Yutaka, Ohshima Toshio, Hirai Syu-ichi, Nakamura Fumio, Taniguchi Masahiko, Mikoshiba Katsuhiko, Honnorat Jérôme, Kolattukudy Pappachan, Thomasset Nicole, Takei Kohtaro, Takahashi Takuya, Goshima Yoshio
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
J Neurosci. 2006 Dec 20;26(51):13357-62. doi: 10.1523/JNEUROSCI.4276-06.2006.
Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that mediates signal transduction of axon guidance molecules. Here, we show evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal migration in the cerebral cortex. In crmp1-/- mice, radial migration of cortical neurons was retarded. This phenotype was not observed in the sema3A-/- and crmp1+/-;sema3A+/- cortices. However, CRMP1 was colocalized with disabled-1 (Dab1), an adaptor protein in Reln signaling. In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype. In addition to axon guidance, CRMP1 regulates neuronal migration by mediating Reln signaling.
塌陷反应介导蛋白1（CRMP1）是介导轴突导向分子信号转导的CRMP家族成员之一。在此，我们展示了CRMP1参与Reelin（Reln）信号传导以调节大脑皮质中神经元迁移的证据。在crmp1基因敲除小鼠中，皮质神经元的放射状迁移受到阻碍。在sema3A基因敲除小鼠以及crmp1杂合子;sema3A杂合子皮质中未观察到这种表型。然而，CRMP1与Disabled-1（Dab1）共定位，Dab1是Reln信号传导中的衔接蛋白。在Reln(rl/rl)皮质中，CRMP1和Dab1表达水平较高，但酪氨酸磷酸化水平较低。在dab1杂合背景下缺失crmp1会导致海马分层破坏，呈现出类似Reeler小鼠的表型。除了轴突导向作用外，CRMP1还通过介导Reln信号传导来调节神经元迁移。
