Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.

Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
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DOI:
10.1371/journal.pone.0226538
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Takeuchi JK
Takeuchi JK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takeuchi M;Takeuchi K;Takai T;Yamaguchi R;Furukawa T;Akagi KI;Takeuchi JK

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Glypican-5 (GPC5)是一种定位于质膜的硫酸肝素蛋白多糖(HSPG)。我们之前报道过,在人间充质干细胞系UE6E7T-3中,GPC5在转化过程中过表达,并通过作为Sonic hedgehog信号的共受体促进细胞增殖。在本研究中,我们利用免疫荧光显微镜发现,在转化细胞(U3DT)中,GPC5不仅定位于细胞表面的初级纤毛,还定位于迁移细胞的前沿、细胞分裂过程中的细胞间桥和泡以及细胞外囊泡。在每个亚细胞区域,GPC5与成纤维细胞生长因子受体(FGFR)和小gtpase Rab11和ARF6共定位,表明GPC5是通过Rab11相关的循环内体传递到这些区域的。这些共定位表明GPC5在FGF2刺激细胞迁移中起重要作用,而GPC5的敲低则可以消除这一作用。我们的研究结果表明,GPC5在U3DT细胞迁移的调控中发挥作用,并为未来研究阐明GPC5的功能提供了一些见解。
Glypican-5 (GPC5) is a heparan sulfate proteoglycan (HSPG) localized to the plasma membrane. We previously reported that in the human mesenchymal stem cell line UE6E7T-3, GPC5 is overexpressed in association with transformation and promotes cell proliferation by acting as a co-receptor for Sonic hedgehog signaling. In this study, we found using immunofluorescence microscopy that in transformed cells (U3DT), GPC5 localized not only at primary cilia on the cell surface, but also at the leading edge of migrating cells, at the intercellular bridge and blebs during cytokinesis, and in extracellular vesicles. In each subcellular region, GPC5 colocalized with fibroblast growth factor receptor (FGFR) and the small GTPases Rab11 and ARF6, indicating that GPC5 is delivered to these regions by Rab11-associated recycling endosomes. These colocalizations suggest that GPC5 plays an important role in FGF2 stimulation of cell migration, which was abrogated by knockdown of GPC5. Our findings indicate that GPC5 plays a role in regulation of U3DT cell migration and provides several insights into the functions of GPC5 that could be elucidated by future studies.
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