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

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 hed...

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Main Authors: Masao Takeuchi, Kikuko Takeuchi, Tomoyo Takai, Ritsuko Yamaguchi, Tetsushi Furukawa, Ken-Ichi Akagi, Jun K Takeuchi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0226538
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author Masao Takeuchi
Kikuko Takeuchi
Tomoyo Takai
Ritsuko Yamaguchi
Tetsushi Furukawa
Ken-Ichi Akagi
Jun K Takeuchi
author_facet Masao Takeuchi
Kikuko Takeuchi
Tomoyo Takai
Ritsuko Yamaguchi
Tetsushi Furukawa
Ken-Ichi Akagi
Jun K Takeuchi
author_sort Masao Takeuchi
collection DOAJ
description 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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spelling doaj.art-d3ba6654f8ca4b51822f78bacf81d4c42022-12-22T04:05:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e022653810.1371/journal.pone.0226538Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.Masao TakeuchiKikuko TakeuchiTomoyo TakaiRitsuko YamaguchiTetsushi FurukawaKen-Ichi AkagiJun K TakeuchiGlypican-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.https://doi.org/10.1371/journal.pone.0226538
spellingShingle Masao Takeuchi
Kikuko Takeuchi
Tomoyo Takai
Ritsuko Yamaguchi
Tetsushi Furukawa
Ken-Ichi Akagi
Jun K Takeuchi
Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
PLoS ONE
title Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
title_full Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
title_fullStr Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
title_full_unstemmed Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
title_short Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT.
title_sort subcellular localization of glypican 5 is associated with dynamic motility of the human mesenchymal stem cell line u3dt
url https://doi.org/10.1371/journal.pone.0226538
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