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...

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Main Authors:	Vaggi, Federico, Disanza, Andrea, Milanesi, Francesca, Di Fiore, Pier Paolo, Menna, Elisabetta, Matteoli, Michela, Gov, Nir S., Scita, Giorgio, Ciliberto, Andrea
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140970/

id	pubmed-3140970
recordtype	oai_dc
spelling	pubmed-31409702011-08-03 The Eps8/IRSp53/VASP Network Differentially Controls Actin Capping and Bundling in Filopodia Formation Vaggi, Federico Disanza, Andrea Milanesi, Francesca Di Fiore, Pier Paolo Menna, Elisabetta Matteoli, Michela Gov, Nir S. Scita, Giorgio Ciliberto, Andrea Research Article 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. Public Library of Science 2011-07-21 /pmc/articles/PMC3140970/ /pubmed/21814501 http://dx.doi.org/10.1371/journal.pcbi.1002088 Text en Vaggi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
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	Vaggi, Federico Disanza, Andrea Milanesi, Francesca Di Fiore, Pier Paolo Menna, Elisabetta Matteoli, Michela Gov, Nir S. Scita, Giorgio Ciliberto, Andrea
spellingShingle	Vaggi, Federico Disanza, Andrea Milanesi, Francesca Di Fiore, Pier Paolo Menna, Elisabetta Matteoli, Michela Gov, Nir S. Scita, Giorgio Ciliberto, Andrea The Eps8/IRSp53/VASP Network Differentially Controls Actin Capping and Bundling in Filopodia Formation
author_facet	Vaggi, Federico Disanza, Andrea Milanesi, Francesca Di Fiore, Pier Paolo Menna, Elisabetta Matteoli, Michela Gov, Nir S. Scita, Giorgio Ciliberto, Andrea
author_sort	Vaggi, Federico
title	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_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_sort	eps8/irsp53/vasp network differentially controls actin capping and bundling in filopodia formation
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.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140970/
_version_	1611466669186613248

The Eps8/IRSp53/VASP Network Differentially Controls Actin Capping and Bundling in Filopodia Formation

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