Lack of Paxillin phosphorylation promotes single-cell migration in vivo.
Lack of Paxillin phosphorylation promotes single-cell migration in vivo.
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DOI：
10.1083/jcb.202206078
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发表时间：
2023-03-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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Xue等人开发了一种系统，用于可视化和比较动物模型与细胞培养系统中单细胞迁移期间的粘着斑形成和动力学。它们揭示了关键粘着斑蛋白调节的根本差异。局灶性粘连是将细胞与细胞外基质物理连接以进行细胞迁移的结构。虽然细胞培养研究提供了丰富的信息，关于局灶性粘连生物学，它是至关重要的，以了解局灶性粘连是如何在其天然环境中动态调节。我们开发了一个斑马鱼系统，在体内单细胞迁移过程中可视化粘着斑结构。我们发现，一个关键的磷酸化位点（Y118）的桩蛋白表现出减少磷酸化迁移细胞在体内相比，在体外。此外，Y118-桩蛋白的非磷酸化形式的表达增加了粘着斑分解并促进了体内细胞迁移，尽管在体外抑制了细胞迁移。使用小鼠模型，我们进一步发现，上游激酶，粘着斑激酶，在体内细胞中下调，表达非磷酸化Y118-桩蛋白的细胞表现出CRKII-DOCK 180/RacGEF途径的激活增加。我们的研究结果提供了重要的新的洞察力的内在调节局灶性粘连细胞迁移在其原生环境。
Xue et al. develop a system to visualize and compare focal adhesion formation and dynamics during single-cell migration in animal models versus cell culture systems. They reveal fundamental differences in the regulation of key focal adhesion proteins. Focal adhesions are structures that physically link the cell to the extracellular matrix for cell migration. Although cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish system to visualize focal adhesion structures during single-cell migration in vivo. We find that a key site of phosphoregulation (Y118) on Paxillin exhibits reduced phosphorylation in migrating cells in vivo compared to in vitro. Furthermore, expression of a non-phosphorylatable version of Y118-Paxillin increases focal adhesion disassembly and promotes cell migration in vivo, despite inhibiting cell migration in vitro. Using a mouse model, we further find that the upstream kinase, focal adhesion kinase, is downregulated in cells in vivo, and cells expressing non-phosphorylatable Y118-Paxillin exhibit increased activation of the CRKII-DOCK180/RacGEF pathway. Our findings provide significant new insight into the intrinsic regulation of focal adhesions in cells migrating in their native environment.
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细胞迁移的基于丝状的接触刺激驱动组织形态发生。
影响因子：
16.6
作者：
Bischoff MC;Lieb S;Renkawitz-Pohl R;Bogdan S
通讯作者：
Bogdan S
DOI：
10.1111/febs.14195
发表时间：
2017-10
期刊：
The FEBS journal
影响因子：
--
作者：
Burridge K
通讯作者：
Burridge K
影响因子：
3.3
作者：
Deakin NO;Turner CE
通讯作者：
Turner CE
影响因子：
6.6
作者：
Geraldo, Sara;Simon, Anthony;Vignjevic, Danijela M.
通讯作者：
Vignjevic, Danijela M.
影响因子：
21.3
作者：
Case, Lindsay B.;Baird, Michelle A.;Shtengel, Gleb;Campbell, Sharon L.;Hess, Harald F.;Davidson, Michael W.;Waterman, Clare M.
通讯作者：
Waterman, Clare M.