The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation.
There is a body of literature that describes the geometry and the physics of filopodia using either stochastic models or partial differential equations and elasticity and coarse-grained theory. Comparatively, there is a paucity of models focusing on the regulation of the network of proteins that con...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-07-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002088&type=printable |
| _version_ | 1826799424059211776 |
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| author | Federico Vaggi Andrea Disanza Francesca Milanesi Pier Paolo Di Fiore Elisabetta Menna Michela Matteoli Nir S Gov Giorgio Scita Andrea Ciliberto |
| author_facet | Federico Vaggi Andrea Disanza Francesca Milanesi Pier Paolo Di Fiore Elisabetta Menna Michela Matteoli Nir S Gov Giorgio Scita Andrea Ciliberto |
| author_sort | Federico Vaggi |
| collection | DOAJ |
| description | There is a body of literature that describes the geometry and the physics of filopodia using either stochastic models or partial differential equations and elasticity and coarse-grained theory. Comparatively, there is a paucity of models focusing on the regulation of the network of proteins that control the formation of different actin structures. Using a combination of in-vivo and in-vitro experiments together with a system of ordinary differential equations, we focused on a small number of well-characterized, interacting molecules involved in actin-dependent filopodia formation: the actin remodeler Eps8, whose capping and bundling activities are a function of its ligands, Abi-1 and IRSp53, respectively; VASP and Capping Protein (CP), which exert antagonistic functions in controlling filament elongation. The model emphasizes the essential role of complexes that contain the membrane deforming protein IRSp53, in the process of filopodia initiation. This model accurately accounted for all observations, including a seemingly paradoxical result whereby genetic removal of Eps8 reduced filopodia in HeLa, but increased them in hippocampal neurons, and generated quantitative predictions, which were experimentally verified. The model further permitted us to explain how filopodia are generated in different cellular contexts, depending on the dynamic interaction established by Eps8, IRSp53 and VASP with actin filaments, thus revealing an unexpected plasticity of the signaling network that governs the multifunctional activities of its components in the formation of filopodia. |
| first_indexed | 2024-12-14T17:05:27Z |
| format | Article |
| id | doaj.art-b68d4bc1cbf4406c94c786b5380e4b0c |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2025-03-17T00:34:51Z |
| publishDate | 2011-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-b68d4bc1cbf4406c94c786b5380e4b0c2025-02-21T05:31:57ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-07-0177e100208810.1371/journal.pcbi.1002088The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation.Federico VaggiAndrea DisanzaFrancesca MilanesiPier Paolo Di FioreElisabetta MennaMichela MatteoliNir S GovGiorgio ScitaAndrea CilibertoThere is a body of literature that describes the geometry and the physics of filopodia using either stochastic models or partial differential equations and elasticity and coarse-grained theory. Comparatively, there is a paucity of models focusing on the regulation of the network of proteins that control the formation of different actin structures. Using a combination of in-vivo and in-vitro experiments together with a system of ordinary differential equations, we focused on a small number of well-characterized, interacting molecules involved in actin-dependent filopodia formation: the actin remodeler Eps8, whose capping and bundling activities are a function of its ligands, Abi-1 and IRSp53, respectively; VASP and Capping Protein (CP), which exert antagonistic functions in controlling filament elongation. The model emphasizes the essential role of complexes that contain the membrane deforming protein IRSp53, in the process of filopodia initiation. This model accurately accounted for all observations, including a seemingly paradoxical result whereby genetic removal of Eps8 reduced filopodia in HeLa, but increased them in hippocampal neurons, and generated quantitative predictions, which were experimentally verified. The model further permitted us to explain how filopodia are generated in different cellular contexts, depending on the dynamic interaction established by Eps8, IRSp53 and VASP with actin filaments, thus revealing an unexpected plasticity of the signaling network that governs the multifunctional activities of its components in the formation of filopodia.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002088&type=printable |
| spellingShingle | Federico Vaggi Andrea Disanza Francesca Milanesi Pier Paolo Di Fiore Elisabetta Menna Michela Matteoli Nir S Gov Giorgio Scita Andrea Ciliberto The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. PLoS Computational Biology |
| title | The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. |
| title_full | The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. |
| title_fullStr | The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. |
| title_full_unstemmed | The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. |
| title_short | The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. |
| title_sort | eps8 irsp53 vasp network differentially controls actin capping and bundling in filopodia formation |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002088&type=printable |
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