title: Distinct predictive performance of Rac1 and Cdc42 in cell migration.
abstract: 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.
authors.affiliation: Graduate School of Informatics, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Yamao
authors.affiliation: Imaging Platform for Spatio-temporal Information, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Honda
authors.initials: H
authors.lastname: Naoki
authors.affiliation: Graduate School of Science, University of Tokyo, Bunkyo, Tokyo, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kunida
authors.affiliation: Imaging Platform for Spatio-temporal Information, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Imaging Platform for Spatio-temporal Information, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.|Graduate School of Biostudies, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Graduate School of Informatics, Kyoto University, Sakyo, Kyoto, Japan.|Imaging Platform for Spatio-temporal Information, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishii
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D022081:Cell Surface Extensions / Q000235:genetics; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D059008:Time-Lapse Imaging; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein