Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.
Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.
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DOI：
10.1038/s41467-018-03512-5
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发表时间：
2018-03-19
影响因子：
16.6
通讯作者：
Liu KJ
中科院分区：
文献类型：
--
作者：
Gonzalez Malagon SG;Lopez Muñoz AM;Doro D;Bolger TG;Poon E;Tucker ER;Adel Al-Lami H;Krause M;Phiel CJ;Chesler L;Liu KJ
神经嵴迁移对其生理功能至关重要。控制哺乳动物神经嵴迁移的机制相对未知，因为很难在体内获得这种细胞群。本研究报告了糖原合成酶激酶3 （GSK3）在调节爪蟾和小鼠神经嵴中的作用。我们证明GSK3在小鼠神经嵴细胞中被酪氨酸磷酸化（pY）， GSK3的缺失导致pFAK增加，以及细胞迁移的关键调节因子Rac1和lamellipodin的失调。GSK3基因的减少导致迁移失败。我们发现pY-GSK3磷酸化依赖于间变性淋巴瘤激酶（ALK），一种与神经母细胞瘤相关的蛋白。与此一致的是，ALK活性增加的神经母细胞瘤细胞表达高水平的pY-GSK3，阻断GSK3或ALK可影响这些细胞的迁移。总之，这项工作确定了GSK3在神经嵴发育和癌症期间细胞迁移中的作用。神经嵴发育缺陷导致神经嵴病变和癌症，但是什么调控这一现象尚不清楚。在这里，作者表明糖原合成酶激酶3 （GSK3）调节神经嵴细胞的迁移，如小鼠GSK3基因缺失所示，这是通过间变性淋巴瘤激酶起作用的。
Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK3 results in failure of migration. We find that pY-GSK3 phosphorylation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with increased ALK activity express high levels of pY-GSK3, and blockade of GSK3 or ALK can affect migration of these cells. Altogether, this work identifies a role for GSK3 in cell migration during neural crest development and cancer. Defects in neural crest development cause neurocristopathies and cancer, but what regulates this is unclear. Here, the authors show that glycogen synthase kinase 3 (GSK3) regulates migration of neural crest cells, as shown on genetic deletion of GSK3 in the mouse, and that this acts via anaplastic lymphoma kinase.
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影响因子：
3.7
作者：
Barrell WB;Szabo-Rogers HL;Liu KJ
通讯作者：
Liu KJ
影响因子：
2.7
作者：
Chang, CB;Hemmati-Brivanlou, A
通讯作者：
Hemmati-Brivanlou, A
影响因子：
5.6
作者：
Jacamo, Rodrigo;Jiang, Xiaohua;Rozengurt, Enrique
通讯作者：
Rozengurt, Enrique
影响因子：
11.4
作者：
HUGHES, K;NIKOLAKAKI, E;WOODGETT, JR
通讯作者：
WOODGETT, JR
影响因子：
5.7
作者：
Christensen, James G.;Zou, Helen Y.;Los, Gerrit
通讯作者：
Los, Gerrit