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Involvement of Girdin in the Determination of Cell Polarity during Cell Migration

Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of act...

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Autores principales: Ohara, Kei, Enomoto, Atsushi, Kato, Takuya, Hashimoto, Takahiko, Isotani-Sakakibara, Mayu, Asai, Naoya, Ishida-Takagishi, Maki, Weng, Liang, Nakayama, Masanori, Watanabe, Takashi, Kato, Katsuhiro, Kaibuchi, Kozo, Murakumo, Yoshiki, Hirooka, Yoshiki, Goto, Hidemi, Takahashi, Masahide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344933/
https://www.ncbi.nlm.nih.gov/pubmed/22574214
http://dx.doi.org/10.1371/journal.pone.0036681
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author Ohara, Kei
Enomoto, Atsushi
Kato, Takuya
Hashimoto, Takahiko
Isotani-Sakakibara, Mayu
Asai, Naoya
Ishida-Takagishi, Maki
Weng, Liang
Nakayama, Masanori
Watanabe, Takashi
Kato, Katsuhiro
Kaibuchi, Kozo
Murakumo, Yoshiki
Hirooka, Yoshiki
Goto, Hidemi
Takahashi, Masahide
author_facet Ohara, Kei
Enomoto, Atsushi
Kato, Takuya
Hashimoto, Takahiko
Isotani-Sakakibara, Mayu
Asai, Naoya
Ishida-Takagishi, Maki
Weng, Liang
Nakayama, Masanori
Watanabe, Takashi
Kato, Katsuhiro
Kaibuchi, Kozo
Murakumo, Yoshiki
Hirooka, Yoshiki
Goto, Hidemi
Takahashi, Masahide
author_sort Ohara, Kei
collection PubMed
description Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.
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spelling pubmed-33449332012-05-09 Involvement of Girdin in the Determination of Cell Polarity during Cell Migration Ohara, Kei Enomoto, Atsushi Kato, Takuya Hashimoto, Takahiko Isotani-Sakakibara, Mayu Asai, Naoya Ishida-Takagishi, Maki Weng, Liang Nakayama, Masanori Watanabe, Takashi Kato, Katsuhiro Kaibuchi, Kozo Murakumo, Yoshiki Hirooka, Yoshiki Goto, Hidemi Takahashi, Masahide PLoS One Research Article Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement. Public Library of Science 2012-05-04 /pmc/articles/PMC3344933/ /pubmed/22574214 http://dx.doi.org/10.1371/journal.pone.0036681 Text en Ohara et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ohara, Kei
Enomoto, Atsushi
Kato, Takuya
Hashimoto, Takahiko
Isotani-Sakakibara, Mayu
Asai, Naoya
Ishida-Takagishi, Maki
Weng, Liang
Nakayama, Masanori
Watanabe, Takashi
Kato, Katsuhiro
Kaibuchi, Kozo
Murakumo, Yoshiki
Hirooka, Yoshiki
Goto, Hidemi
Takahashi, Masahide
Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title_full Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title_fullStr Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title_full_unstemmed Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title_short Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
title_sort involvement of girdin in the determination of cell polarity during cell migration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344933/
https://www.ncbi.nlm.nih.gov/pubmed/22574214
http://dx.doi.org/10.1371/journal.pone.0036681
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