Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration.
Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration.
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DOI：
10.1016/j.ydbio.2008.12.006
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发表时间：
2009-03-01
影响因子：
2.7
通讯作者：
Strickland, Sidney
中科院分区：
文献类型：
--
作者：
Chen, Zu-Lin;Haegeli, Veronique;Yu, Huaxu;Strickland, Sidney
层粘连蛋白在体外对神经元具有显着且多样的作用。然而，它们在大脑发育中的体内功能尚不清楚。在这里，我们发现大脑皮层层粘连蛋白 γ1 的敲除会导致神经突发生和神经元迁移的缺陷。在突变小鼠中，皮质层结构被破坏，轴突寻路受损。在发育过程中，层粘连蛋白表达的丧失会损害 FAK 和桩蛋白的磷酸化，表明整合素信号通路存在缺陷。此外，突变皮质中 GSK-3β 的磷酸化和蛋白水平均显着降低，但仅 AKT 的磷酸化受到影响。体外层粘连蛋白γ1表达的敲除可显着抑制神经突的生长。这些结果表明，层粘连蛋白通过 AKT/GSK-3β 途径的整合素信号传导调节神经突生长和神经元迁移，从而揭示了层粘连蛋白在大脑发育中功能的新机制。
Laminins have dramatic and varied actions on neurons in vitro. However, their in vivo function in brain development is not clear. Here we show that knockout of laminin γ1 in the cerebral cortex leads to defects in neuritogenesis and neuronal migration. In the mutant mice, cortical layer structures were disrupted, and axonal pathfinding was impaired. During development, loss of laminin expression impaired phosphorylation of FAK and paxillin, indicating defects in integrin signaling pathways. Moreover, both phosphorylation and protein levels of GSK-3β were significantly decreased, but only phosphorylation of AKT was affected in the mutant cortex. Knockout of laminin γ1 expression in vitro, dramatically inhibited neurite growth. These results indicate that laminin regulates neurite growth and neuronal migration via integrin signaling through the AKT/GSK-3β pathway, and thus reveal a novel mechanism of laminin function in brain development.
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影响因子：
3.3
作者：
Indyk, JA;Chen, ZL;Strickland, S
通讯作者：
Strickland, S
影响因子：
3.7
作者：
deCurtis, I;Malanchini, B
通讯作者：
Malanchini, B
p38mapk对帕西林的磷酸化参与PC-12细胞的神经突延伸。
DOI：
10.1083/jcb.200307081
发表时间：
2004-02-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Huang C;Borchers CH;Schaller MD;Jacobson K
通讯作者：
Jacobson K
影响因子：
21.3
作者：
Ivankovic-Dikic, I;Grönroos, E;Dikic, I
通讯作者：
Dikic, I
影响因子：
3.3
作者：
Chen, ZL;Indyk, JA;Strickland, S
通讯作者：
Strickland, S