Distinct predictive performance of Rac1 and Cdc42 in cell migration

We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response func...

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Main Authors:	Yamao, Masataka, Naoki, Honda, Kunida, Katsuyuki, Aoki, Kazuhiro, Matsuda, Michiyuki, Ishii, Shin
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669460/

id	pubmed-4669460
recordtype	oai_dc
spelling	pubmed-46694602015-12-09 Distinct predictive performance of Rac1 and Cdc42 in cell migration Yamao, Masataka Naoki, Honda Kunida, Katsuyuki Aoki, Kazuhiro Matsuda, Michiyuki Ishii, Shin Article We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration. Nature Publishing Group 2015-12-04 /pmc/articles/PMC4669460/ /pubmed/26634649 http://dx.doi.org/10.1038/srep17527 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yamao, Masataka Naoki, Honda Kunida, Katsuyuki Aoki, Kazuhiro Matsuda, Michiyuki Ishii, Shin
spellingShingle	Yamao, Masataka Naoki, Honda Kunida, Katsuyuki Aoki, Kazuhiro Matsuda, Michiyuki Ishii, Shin Distinct predictive performance of Rac1 and Cdc42 in cell migration
author_facet	Yamao, Masataka Naoki, Honda Kunida, Katsuyuki Aoki, Kazuhiro Matsuda, Michiyuki Ishii, Shin
author_sort	Yamao, Masataka
title	Distinct predictive performance of Rac1 and Cdc42 in cell migration
title_short	Distinct predictive performance of Rac1 and Cdc42 in cell migration
title_full	Distinct predictive performance of Rac1 and Cdc42 in cell migration
title_fullStr	Distinct predictive performance of Rac1 and Cdc42 in cell migration
title_full_unstemmed	Distinct predictive performance of Rac1 and Cdc42 in cell migration
title_sort	distinct predictive performance of rac1 and cdc42 in cell migration
description	We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669460/
_version_	1613509451271110656

Distinct predictive performance of Rac1 and Cdc42 in cell migration

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