Syndecan-4 Modulates Cell Polarity and Migration by Influencing Centrosome Positioning and Intracellular Calcium Distribution.
Syndecan-4 Modulates Cell Polarity and Migration by Influencing Centrosome Positioning and Intracellular Calcium Distribution.
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DOI：
10.3389/fcell.2020.575227
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发表时间：
2020
影响因子：
5.5
通讯作者：
Keller-Pinter A
中科院分区：
文献类型：
--
作者：
Becsky D;Szabo K;Gyulai-Nagy S;Gajdos T;Bartos Z;Balind A;Dux L;Horvath P;Erdelyi M;Homolya L;Keller-Pinter A
有效的细胞迁移需要细胞极化，其特征是前后边缘的形成，细胞核的适当定位以及高尔基体和中心体向前缘的重新定向。迁移还需要一个不对称的前后钙（Ca2+）梯度的发展，以调节焦点粘附组装和肌动球蛋白收缩性。在这里，我们证明了syndecan-4（一种跨膜硫酸肝素蛋白多糖）的沉默会干扰迁移的哺乳动物成肌细胞（即激活的卫星干细胞）的正确极化。特别是，syndecan-4敲低完全消除了细胞内Ca2+梯度，取消了中心体重定向，从而降低了细胞运动，证明了syndecan-4在细胞极性中的作用。此外，syndecan-4在迁移过程中呈现极化分布。Syndecan-4敲低细胞在定向迁移过程中的总移动距离、从起点的最大和矢量距离以及平均和最大细胞速度均有所减少。syndecan-4敲除细胞的超分辨率直接随机光学重建显微镜图像显示，肌动蛋白细胞骨架结构发生了纳米级的变化，如迁移细胞板足中分支数量和单个分支长度的减少。考虑到成肌细胞迁移在胚胎发育和出生后肌肉再生过程中的重要性，我们得出结论，我们的研究结果可以促进对这些过程的理解，以及syndecan-4在细胞迁移过程中的一般作用。
Efficient cell migration requires cellular polarization, which is characterized by the formation of leading and trailing edges, appropriate positioning of the nucleus and reorientation of the Golgi apparatus and centrosomes toward the leading edge. Migration also requires the development of an asymmetrical front-to-rear calcium (Ca2+) gradient to regulate focal adhesion assembly and actomyosin contractility. Here we demonstrate that silencing of syndecan-4, a transmembrane heparan sulfate proteoglycan, interferes with the correct polarization of migrating mammalian myoblasts (i.e., activated satellite stem cells). In particular, syndecan-4 knockdown completely abolished the intracellular Ca2+ gradient, abrogated centrosome reorientation and thus decreased cell motility, demonstrating the role of syndecan-4 in cell polarity. Additionally, syndecan-4 exhibited a polarized distribution during migration. Syndecan-4 knockdown cells exhibited decreases in the total movement distance during directional migration, maximum and vectorial distances from the starting point, as well as average and maximum cell speeds. Super-resolution direct stochastic optical reconstruction microscopy images of syndecan-4 knockdown cells revealed nanoscale changes in the actin cytoskeletal architecture, such as decreases in the numbers of branches and individual branch lengths in the lamellipodia of the migrating cells. Given the crucial importance of myoblast migration during embryonic development and postnatal muscle regeneration, we conclude that our results could facilitate an understanding of these processes and the general role of syndecan-4 during cell migration.
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影响因子：
64.5
作者：
Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A
影响因子：
8
作者：
Keller-Pinter, Aniko;Bottka, Sandor;Szilak, Laszlo
通讯作者：
Szilak, Laszlo
DOI：
10.1016/j.bbagen.2009.07.015
发表时间：
2009-10-01
影响因子：
3
作者：
Charni, Faten;Friand, Veronique;Sutton, Angela
通讯作者：
Sutton, Angela
影响因子：
3.5
作者：
Keller-Pinter, Aniko;Szabo, Kitti;Dux, Laszlo
通讯作者：
Dux, Laszlo
影响因子：
15.9
作者：
Echtermeyer, F;Streit, M;Goetinck, PF
通讯作者：
Goetinck, PF