Gβ1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium.
Gβ1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium.
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DOI：
10.1016/j.ydbio.2013.10.027
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发表时间：
2014-01-15
影响因子：
2.7
通讯作者：
Lin, Fang
中科院分区：
文献类型：
--
作者：
Xu, Hui;Ye, Ding;Behra, Martine;Burgess, Shawn;Chen, Songhai;Lin, Fang
集体细胞迁移对于正常发育、组织修复和癌症转移至关重要。后侧线原基（pLLP）的迁移产生斑马鱼感觉器官（神经乳突，NM）。这种迁移由pLLP前缘的前导细胞促进，其表达G蛋白偶联趋化因子受体Cxcr 4 b并响应趋化因子Cxcl 12 a。然而，Cxc 112 a/Cxcr 4 b信号调节pLLP迁移的机制仍不清楚。在这里，我们报告，信号转导的异源三聚体G蛋白亚基Gβ1是必不可少的适当pLLP迁移。虽然Gβ1和Gβ4在pLLP和NM中均表达，但Gβ1而非Gβ4的缺失导致pLLP迁移停滞。在缺乏Gβ1的胚胎中，pLLP细胞以不协调的方式迁移，并且不能在前沿延伸突起，表型模仿那些缺乏Cxcl 12 a或Cxcr 4 b的胚胎。移植试验表明，与Cxcr 4 b一样，Gβ1仅在pLLP的前导细胞中需要。对pLLP中F-肌动蛋白动力学的分析表明，野生型前导细胞在pLLP迁移方向上显示出广泛的肌动蛋白聚合，而Gβ1、Cxcr 4 b或Cxcl 12 a缺陷的对应细胞则没有。最后，协同实验表明Gβ1和Cxcr 4 b在调节pLLP迁移中存在遗传相互作用。总的来说，我们的数据表明，Gβ1控制pLLP的迁移，可能是通过作用于Cxcl 12 a/Cxcr 4 b信号传导的下游。这项研究也为Gβ亚型在体内的功能特异性提供了有力的证据。
Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxc112a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit Gβ1 is essential for proper pLLP migration. Although both Gβ1 and Gβ4 are expressed in the pLLP and NMs, depletion of Gβ1 but not Gβ4 resulted in an arrest of pLLP migration. In embryos deficient for Gβ1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, Gβ1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for Gβ1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that Gβ1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that Gβ1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among Gβ isoforms in vivo.
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影响因子：
4.5
作者：
Behra M;Bradsher J;Sougrat R;Gallardo V;Allende ML;Burgess SM
通讯作者：
Burgess SM
DOI：
10.1073/pnas.252339399
发表时间：
2002-12-10
影响因子：
11.1
作者：
David, NB;Sapède, D;Ghysen, A
通讯作者：
Ghysen, A
影响因子：
--
作者：
Dambly-Chaudière C;Cubedo N;Ghysen A
通讯作者：
Ghysen A
影响因子：
64.5
作者：
Doitsidou, M;Reichman-Fried, M;Raz, E
通讯作者：
Raz, E
影响因子：
11.8
作者：
Aman, Andy;Piotrowski, Tatjana
通讯作者：
Piotrowski, Tatjana