Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration.
Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration.
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DOI：
10.1371/journal.pone.0060193
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Christensen ST
中科院分区：
文献类型：
--
作者：
Veland IR;Montjean R;Eley L;Pedersen LB;Schwab A;Goodship J;Kristiansen K;Pedersen SF;Saunier S;Christensen ST
反转蛋白是一种纤毛蛋白，其部分地通过降解Dishevelled（Dvl）蛋白以协调平面细胞极性（PCP）中的Wnt信号传导来关键地调节脊椎动物中的发育过程和组织稳态。在这里，我们研究了逆转蛋白在协调细胞迁移中的作用，这高度依赖于单细胞水平的极性过程，包括细胞骨架的空间和时间组织以及迁移细胞前缘形成中蛋白质的表达和细胞定位。使用来自inv−/−和inv+/+动物的小鼠胚胎成纤维细胞（MEFs）培养物，我们证实了inv−/−和inv+/+ MEFs都形成初级纤毛，并且Inversin定位于inv+/+ MEFs中的初级纤毛。在伤口愈合试验中，inv−/− MEFs的迁移能力严重受损，并表现出细胞骨架重排，包括扭曲的板状伪足形成和纤毛定向。转录组分析显示，与inv+/+ MEFs相比，inv−/− MEFs中Wnt信号传导和调节肌动蛋白组织和粘着斑的途径失调。此外，Dvl-1和Dvl-3定位于MEF初级纤毛，并且β-连环蛋白/Wnt信号在inv−/− MEF中升高，这进一步显示Dvl-3的纤毛定位减少。最后，inv−/− MEFs显示RhoA、Rac 1和Cdc 42 GTP酶的活性和定位发生了显著改变，Na+/H+交换器NHE 1和ezrin/radixin/moesin（ERM）蛋白的表达异常，并靶向伤口边缘的细胞。在表达Inv-GFP的inv−/− MEFs中，纤毛基部的β-连环蛋白磷酸化和明确的板状伪足的形成以及ERM在迁移细胞前缘的定位和激活得以恢复。总的来说，我们的研究结果指出，在控制细胞迁移过程中，至少部分通过转录调控的基因参与Wnt信号和控制细胞骨架组织和离子转运的途径，反转蛋白的意义。
Inversin is a ciliary protein that critically regulates developmental processes and tissue homeostasis in vertebrates, partly through the degradation of Dishevelled (Dvl) proteins to coordinate Wnt signaling in planar cell polarity (PCP). Here, we investigated the role of Inversin in coordinating cell migration, which highly depends on polarity processes at the single-cell level, including the spatial and temporal organization of the cytoskeleton as well as expression and cellular localization of proteins in leading edge formation of migrating cells. Using cultures of mouse embryonic fibroblasts (MEFs) derived from inv−/− and inv+/+ animals, we confirmed that both inv−/− and inv+/+ MEFs form primary cilia, and that Inversin localizes to the primary cilium in inv+/+ MEFs. In wound healing assays, inv−/− MEFs were severely compromised in their migratory ability and exhibited cytoskeletal rearrangements, including distorted lamellipodia formation and cilia orientation. Transcriptome analysis revealed dysregulation of Wnt signaling and of pathways regulating actin organization and focal adhesions in inv−/− MEFs as compared to inv+/+ MEFs. Further, Dvl-1 and Dvl-3 localized to MEF primary cilia, and β-catenin/Wnt signaling was elevated in inv−/− MEFs, which moreover showed reduced ciliary localization of Dvl-3. Finally, inv−/− MEFs displayed dramatically altered activity and localization of RhoA, Rac1, and Cdc42 GTPases, and aberrant expression and targeting of the Na+/H+ exchanger NHE1 and ezrin/radixin/moesin (ERM) proteins to the edge of cells facing the wound. Phosphorylation of β-catenin at the ciliary base and formation of well-defined lamellipodia with localization and activation of ERM to the leading edge of migrating cells were restored in inv−/− MEFs expressing Inv-GFP. Collectively, our findings point to the significance of Inversin in controlling cell migration processes, at least in part through transcriptional regulation of genes involved in Wnt signaling and pathways that control cytoskeletal organization and ion transport.
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影响因子：
4.8
作者：
Christensen, ST;Guerra, C;Hamasaki, T
通讯作者：
Hamasaki, T
影响因子：
30.8
作者：
Gerdes, Jantje M.;Liu, Yangfan;Katsanis, Nicholas
通讯作者：
Katsanis, Nicholas
影响因子：
3.3
作者：
Cardone, RA;Bagorda, A;Reshkin, SJ
通讯作者：
Reshkin, SJ
影响因子：
4
作者：
Baeyens, Nicolas;de Meester, Carole;Morel, Nicole
通讯作者：
Morel, Nicole
Caveolin-1通过SRC激酶和Rho GTPases调节细胞极化和定向迁移。
DOI：
10.1083/jcb.200701006
发表时间：
2007-05-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Grande-García A;Echarri A;de Rooij J;Alderson NB;Waterman-Storer CM;Valdivielso JM;del Pozo MA
通讯作者：
del Pozo MA