Molecular basis for the dual function of Eps8 on actin dynamics: bundling and capping.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Malabarba, Maria Grazia
Le Clainche, Christophe
Di Fiore, Pier Paolo
MetadataShow full item record
AbstractActin capping and cross-linking proteins regulate the dynamics and architectures of different cellular protrusions. Eps8 is the founding member of a unique family of capping proteins capable of side-binding and bundling actin filaments. However, the structural basis through which Eps8 exerts these functions remains elusive. Here, we combined biochemical, molecular, and genetic approaches with electron microscopy and image analysis to dissect the molecular mechanism responsible for the distinct activities of Eps8. We propose that bundling activity of Eps8 is mainly mediated by a compact four helix bundle, which is contacting three actin subunits along the filament. The capping activity is mainly mediated by a amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers. Single-point mutagenesis validated these modes of binding, permitting us to dissect Eps8 capping from bundling activity in vitro. We further showed that the capping and bundling activities of Eps8 can be fully dissected in vivo, demonstrating the physiological relevance of the identified Eps8 structural/functional modules. Eps8 controls actin-based motility through its capping activity, while, as a bundler, is essential for proper intestinal morphogenesis of developing Caenorhabditis elegans.
CitationMolecular basis for the dual function of Eps8 on actin dynamics: bundling and capping. 2010, 8 (6):e1000387 PLoS Biol.
AffiliationIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
The following license files are associated with this item:
- Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8-IRSp53 complex.
- Authors: Disanza A, Mantoani S, Hertzog M, Gerboth S, Frittoli E, Steffen A, Berhoerster K, Kreienkamp HJ, Milanesi F, Di Fiore PP, Ciliberto A, Stradal TE, Scita G
- Issue date: 2006 Dec
- Ezrin regulates microvillus morphogenesis by promoting distinct activities of Eps8 proteins.
- Authors: Zwaenepoel I, Naba A, Da Cunha MM, Del Maestro L, Formstecher E, Louvard D, Arpin M
- Issue date: 2012 Mar
- Eps8 controls actin-based motility by capping the barbed ends of actin filaments.
- Authors: Disanza A, Carlier MF, Stradal TE, Didry D, Frittoli E, Confalonieri S, Croce A, Wehland J, Di Fiore PP, Scita G
- Issue date: 2004 Dec
- The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation.
- Authors: Vaggi F, Disanza A, Milanesi F, Di Fiore PP, Menna E, Matteoli M, Gov NS, Scita G, Ciliberto A
- Issue date: 2011 Jul
- Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration.
- Authors: Logue JS, Cartagena-Rivera AX, Baird MA, Davidson MW, Chadwick RS, Waterman CM
- Issue date: 2015 Jul 11