ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation

Cell migration is a highly regulated event that is initiated by cell membrane protrusion and actin reorganization. Robo1, a single-pass transmembrane receptor, is crucial for neuronal guidance and cell migration. ADP-ribosylation factor (Arf)–like 4A (Arl4A), an Arf small GTPase, functions in cell m...

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Autores principales: Chiang, Tsai-Shin, Lin, Ming-Chieh, Tsai, Meng-Chen, Chen, Chieh-Hsin, Jang, Li-Ting, Lee, Fang-Jen S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337904/
https://www.ncbi.nlm.nih.gov/pubmed/30427759
http://dx.doi.org/10.1091/mbc.E18-01-0001
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author Chiang, Tsai-Shin
Lin, Ming-Chieh
Tsai, Meng-Chen
Chen, Chieh-Hsin
Jang, Li-Ting
Lee, Fang-Jen S.
author_facet Chiang, Tsai-Shin
Lin, Ming-Chieh
Tsai, Meng-Chen
Chen, Chieh-Hsin
Jang, Li-Ting
Lee, Fang-Jen S.
author_sort Chiang, Tsai-Shin
collection PubMed
description Cell migration is a highly regulated event that is initiated by cell membrane protrusion and actin reorganization. Robo1, a single-pass transmembrane receptor, is crucial for neuronal guidance and cell migration. ADP-ribosylation factor (Arf)–like 4A (Arl4A), an Arf small GTPase, functions in cell morphology, cell migration, and actin cytoskeleton remodeling; however, the molecular mechanisms of Arl4A in cell migration are unclear. Here, we report that the binding of Arl4A to Robo1 modulates cell migration by promoting Cdc42 activation. We found that Arl4A interacts with Robo1 in a GTP-dependent manner and that the Robo1 amino acid residues 1394–1398 are required for this interaction. The Arl4A-Robo1 interaction is essential for Arl4A-induced cell migration and Cdc42 activation but not for the plasma membrane localization of Robo1. In addition, we show that the binding of Arl4A to Robo1 decreases the association of Robo1 with the Cdc42 GTPase-activating protein srGAP1. Furthermore, Slit2/Robo1 binding down-regulates the Arl4A-Robo1 interaction in vivo, thus attenuating Cdc42-mediated cell migration. Therefore, our study reveals a novel mechanism by which Arl4A participates in Slit2/Robo1 signaling to modulate cell motility by regulating Cdc42 activity.
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spelling pubmed-63379042019-03-16 ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation Chiang, Tsai-Shin Lin, Ming-Chieh Tsai, Meng-Chen Chen, Chieh-Hsin Jang, Li-Ting Lee, Fang-Jen S. Mol Biol Cell Articles Cell migration is a highly regulated event that is initiated by cell membrane protrusion and actin reorganization. Robo1, a single-pass transmembrane receptor, is crucial for neuronal guidance and cell migration. ADP-ribosylation factor (Arf)–like 4A (Arl4A), an Arf small GTPase, functions in cell morphology, cell migration, and actin cytoskeleton remodeling; however, the molecular mechanisms of Arl4A in cell migration are unclear. Here, we report that the binding of Arl4A to Robo1 modulates cell migration by promoting Cdc42 activation. We found that Arl4A interacts with Robo1 in a GTP-dependent manner and that the Robo1 amino acid residues 1394–1398 are required for this interaction. The Arl4A-Robo1 interaction is essential for Arl4A-induced cell migration and Cdc42 activation but not for the plasma membrane localization of Robo1. In addition, we show that the binding of Arl4A to Robo1 decreases the association of Robo1 with the Cdc42 GTPase-activating protein srGAP1. Furthermore, Slit2/Robo1 binding down-regulates the Arl4A-Robo1 interaction in vivo, thus attenuating Cdc42-mediated cell migration. Therefore, our study reveals a novel mechanism by which Arl4A participates in Slit2/Robo1 signaling to modulate cell motility by regulating Cdc42 activity. The American Society for Cell Biology 2019-01-01 /pmc/articles/PMC6337904/ /pubmed/30427759 http://dx.doi.org/10.1091/mbc.E18-01-0001 Text en © 2019 Chiang et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Chiang, Tsai-Shin
Lin, Ming-Chieh
Tsai, Meng-Chen
Chen, Chieh-Hsin
Jang, Li-Ting
Lee, Fang-Jen S.
ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title_full ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title_fullStr ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title_full_unstemmed ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title_short ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation
title_sort adp-ribosylation factor–like 4a interacts with robo1 to promote cell migration by regulating cdc42 activation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337904/
https://www.ncbi.nlm.nih.gov/pubmed/30427759
http://dx.doi.org/10.1091/mbc.E18-01-0001
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