Spontaneous signal generation by an excitable system for cell migration
Eukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1373609/full |
| _version_ | 1797293137217978368 |
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| author | Satomi Matsuoka Satomi Matsuoka Satomi Matsuoka Koji Iwamoto Da Young Shin Da Young Shin Masahiro Ueda Masahiro Ueda Masahiro Ueda |
| author_facet | Satomi Matsuoka Satomi Matsuoka Satomi Matsuoka Koji Iwamoto Da Young Shin Da Young Shin Masahiro Ueda Masahiro Ueda Masahiro Ueda |
| author_sort | Satomi Matsuoka |
| collection | DOAJ |
| description | Eukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the migrating cell be generated spontaneously from the intrinsic activities of intracellular signaling networks. Recent studies have identified an excitable system as the mechanism of the spontaneous signal generation. Here, we discuss how the excitable system of Ras, a small G protein, regulates signaling networks in Dictyostelium discoideum as a model organism. The excitability produces a domain where an active form of Ras is enriched on the cell membrane without extracellular directional cues, such that Ras serves as the anterior signal. The typical spatiotemporal characteristics are mathematically explained by reaction-diffusion models. These models further enable a quantitative analysis of the dynamics that depends on the internal cellular states and surrounding environments. Downstream of the Ras excitable system, a phosphoinositide metabolic network composed of PI3K, PTEN, PI(3,4,5)P3 and PI(4,5)P2 exhibits bistability to discretize the anterior and posterior regions of the cell membrane. Upstream, a local excitation and global inhibition local excitation global inhibition network, which works for gradient sensing in the presence of chemoattractant gradients, spatiotemporally biases the excitability of Ras for chemotaxis. In parallel with the Ras excitable system, the cGMP signaling pathway constitutes another excitable system of its own periodicity to ensure flexible migratory dynamics. In addition to these intracellular signaling networks, an intercellular signaling network activated by secreted cAMP is coupled with the Ras excitable system for collective cell migration. Finally, we discuss how the excitable system of Ras operates as a platform of information integration by receiving multiple intrinsic and extrinsic signals to ensure spontaneous cellular activity and robust responses in eukaryotic cell migration under natural complex environments. |
| first_indexed | 2024-03-07T20:08:31Z |
| format | Article |
| id | doaj.art-fbcd236d1c5f435a95e2a93b457b72bf |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-07T20:08:31Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fbcd236d1c5f435a95e2a93b457b72bf2024-02-28T04:18:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-02-011210.3389/fcell.2024.13736091373609Spontaneous signal generation by an excitable system for cell migrationSatomi Matsuoka0Satomi Matsuoka1Satomi Matsuoka2Koji Iwamoto3Da Young Shin4Da Young Shin5Masahiro Ueda6Masahiro Ueda7Masahiro Ueda8Laboratory of Single Molecule Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanLaboratory of Single Molecule Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Cell Signaling Dynamics, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, JapanLaboratory of Single Molecule Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory of Single Molecule Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Cell Signaling Dynamics, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, JapanLaboratory of Single Molecule Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanLaboratory of Single Molecule Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, JapanLaboratory for Cell Signaling Dynamics, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, JapanEukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the migrating cell be generated spontaneously from the intrinsic activities of intracellular signaling networks. Recent studies have identified an excitable system as the mechanism of the spontaneous signal generation. Here, we discuss how the excitable system of Ras, a small G protein, regulates signaling networks in Dictyostelium discoideum as a model organism. The excitability produces a domain where an active form of Ras is enriched on the cell membrane without extracellular directional cues, such that Ras serves as the anterior signal. The typical spatiotemporal characteristics are mathematically explained by reaction-diffusion models. These models further enable a quantitative analysis of the dynamics that depends on the internal cellular states and surrounding environments. Downstream of the Ras excitable system, a phosphoinositide metabolic network composed of PI3K, PTEN, PI(3,4,5)P3 and PI(4,5)P2 exhibits bistability to discretize the anterior and posterior regions of the cell membrane. Upstream, a local excitation and global inhibition local excitation global inhibition network, which works for gradient sensing in the presence of chemoattractant gradients, spatiotemporally biases the excitability of Ras for chemotaxis. In parallel with the Ras excitable system, the cGMP signaling pathway constitutes another excitable system of its own periodicity to ensure flexible migratory dynamics. In addition to these intracellular signaling networks, an intercellular signaling network activated by secreted cAMP is coupled with the Ras excitable system for collective cell migration. Finally, we discuss how the excitable system of Ras operates as a platform of information integration by receiving multiple intrinsic and extrinsic signals to ensure spontaneous cellular activity and robust responses in eukaryotic cell migration under natural complex environments.https://www.frontiersin.org/articles/10.3389/fcell.2024.1373609/fullexcitable systemspontaneous signal generationRasrandom cell migrationchemotaxis |
| spellingShingle | Satomi Matsuoka Satomi Matsuoka Satomi Matsuoka Koji Iwamoto Da Young Shin Da Young Shin Masahiro Ueda Masahiro Ueda Masahiro Ueda Spontaneous signal generation by an excitable system for cell migration Frontiers in Cell and Developmental Biology excitable system spontaneous signal generation Ras random cell migration chemotaxis |
| title | Spontaneous signal generation by an excitable system for cell migration |
| title_full | Spontaneous signal generation by an excitable system for cell migration |
| title_fullStr | Spontaneous signal generation by an excitable system for cell migration |
| title_full_unstemmed | Spontaneous signal generation by an excitable system for cell migration |
| title_short | Spontaneous signal generation by an excitable system for cell migration |
| title_sort | spontaneous signal generation by an excitable system for cell migration |
| topic | excitable system spontaneous signal generation Ras random cell migration chemotaxis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1373609/full |
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