Cellular Control of Cortical Actin Nucleation
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Notice bibliographique
Résumé
The contractile actin cortex is a thin layer of actin, myosin, and actin-binding proteins that subtends the membrane of animal cells. The cortex is the main determinant of cell shape and plays a fundamental role in cell division [1Stewart M.P. Helenius J. Toyoda Y. Ramanathan S.P. Muller D.J. Hyman A.A. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding.Nature. 2011; 469: 226-230Crossref PubMed Scopus (446) Google Scholar, 2Kunda P. Pelling A.E. Liu T. Baum B. Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis.Curr. Biol. 2008; 18: 91-101Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar, 3Bray D. White J.G. Cortical flow in animal cells.Science. 1988; 239: 883-888Crossref PubMed Scopus (418) Google Scholar], migration [4Cramer L.P. Forming the cell rear first: breaking cell symmetry to trigger directed cell migration.Nat. Cell Biol. 2010; 12: 628-632Crossref PubMed Scopus (84) Google Scholar], and tissue morphogenesis [5Levayer R. Lecuit T. Biomechanical regulation of contractility: spatial control and dynamics.Trends Cell Biol. 2012; 22: 61-81Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar]. For example, cortex contractility plays a crucial role in amoeboid migration of metastatic cells [6Charras G. Paluch E. Blebs lead the way: how to migrate without lamellipodia.Nat. Rev. Mol. Cell Biol. 2008; 9: 730-736Crossref PubMed Scopus (552) Google Scholar] and during division, where its misregulation can lead to aneuploidy [7Sedzinski J. Biro M. Oswald A. Tinevez J.Y. Salbreux G. Paluch E. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow.Nature. 2011; 476: 462-466Crossref PubMed Scopus (247) Google Scholar]. Despite its importance, our knowledge of the cortex is poor, and even the proteins nucleating it remain unknown, though a number of candidates have been proposed based on indirect evidence [8Eisenmann K.M. Harris E.S. Kitchen S.M. Holman H.A. Higgs H.N. Alberts A.S. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex.Curr. Biol. 2007; 17: 579-591Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 9Hannemann S. Madrid R. Stastna J. Kitzing T. Gasteier J. Schönichen A. Bouchet J. Jimenez A. Geyer M. Grosse R. et al.The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing.J. Biol. Chem. 2008; 283: 27891-27903Crossref PubMed Scopus (59) Google Scholar, 10Kitzing T.M. Wang Y. Pertz O. Copeland J.W. Grosse R. Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC.Oncogene. 2010; 29: 2441-2448Crossref PubMed Scopus (115) Google Scholar, 11Kitzing T.M. Sahadevan A.S. Brandt D.T. Knieling H. Hannemann S. Fackler O.T. Grosshans J. Grosse R. Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion.Genes Dev. 2007; 21: 1478-1483Crossref PubMed Scopus (136) Google Scholar, 12Stastna J. Pan X. Wang H. Kollmannsperger A. Kutscheidt S. Lohmann V. Grosse R. Fackler O.T. Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation.Cell Res. 2012; 22: 728-745Crossref PubMed Scopus (20) Google Scholar, 13Derivery E. Fink J. Martin D. Houdusse A. Piel M. Stradal T.E. Louvard D. Gautreau A. Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.PLoS One. 2008; 3: e2462Crossref PubMed Scopus (54) Google Scholar, 14Wyse M.M. Lei J. Nestor-Kalinoski A.L. Eisenmann K.M. Dia-interacting protein (DIP) imposes migratory plasticity in mDia2-dependent tumor cells in three-dimensional matrices.PLoS One. 2012; 7: e45085Crossref PubMed Scopus (16) Google Scholar, 15Tominaga T. Sahai E. Chardin P. McCormick F. Courtneidge S.A. Alberts A.S. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling.Mol. Cell. 2000; 5: 13-25Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar]. Here, we used two independent approaches to identify cortical actin nucleators: a proteomic analysis using cortex-rich isolated blebs, and a localization/small hairpin RNA (shRNA) screen searching for phenotypes with a weakened cortex or altered contractility. This unbiased study revealed that two proteins generated the majority of cortical actin: the formin mDia1 and the Arp2/3 complex. Each nucleator contributed a similar amount of F-actin to the cortex but had very different accumulation kinetics. Electron microscopy examination revealed that each nucleator affected cortical network architecture differently. mDia1 depletion led to failure in division, but Arp2/3 depletion did not. Interestingly, despite not affecting division on its own, Arp2/3 inhibition potentiated the effect of mDia1 depletion. Our findings indicate that the bulk of the actin cortex is nucleated by mDia1 and Arp2/3 and suggest a mechanism for rapid fine-tuning of cortex structure and mechanics by adjusting the relative contribution of each nucleator.
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Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle