Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation
Plasma membrane (PM) blebs are dynamic actin-rich cell protrusions that occur, e.g., during cytokinesis, amoeboid cell motility and cell attachment. Using a targeted siRNA screen against 21 actin nucleation factors, we identify a novel and essential role of the human diaphanous formin DIAPH3 in PM b...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2012
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| In: |
Cell research
Year: 2011, Jahrgang: 22, Heft: 4, Pages: 728-745 |
| ISSN: | 1748-7838 |
| DOI: | 10.1038/cr.2011.202 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1038/cr.2011.202 Verlag, Volltext: https://www.nature.com/articles/cr2011202 
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| Verfasserangaben: | Jana Stastna, Xiaoyu Pan, Haicui Wang, Alina Kollmannsperger, Stefan Kutscheidt, Volker Lohmann, Robert Grosse, Oliver T. Fackler |
| Zusammenfassung: | Plasma membrane (PM) blebs are dynamic actin-rich cell protrusions that occur, e.g., during cytokinesis, amoeboid cell motility and cell attachment. Using a targeted siRNA screen against 21 actin nucleation factors, we identify a novel and essential role of the human diaphanous formin DIAPH3 in PM blebbing during cell adhesion. Suppression of DIAPH3 inhibited blebbing to promote rapid cell spreading involving β1-integrin. Multiple isoforms of DIAPH3 were detected on the mRNA and protein level of which isoforms 3 and 7 were the largest and most abundant isoforms that however did not induce formation of actin-rich protrusions. Rather, PM blebbing specifically involved the low abundance isoform 1 of DIAPH3 and activation of isoform 7 by deletion of the diaphanous-autoregulatory domain caused the formation of filopodia. Dimerization and actin assembly activity were essential for induction of specific cell protrusions by DIAPH3 isoforms 1 and 7. Our data suggest that the N-terminal region comprising the GTPase-binding domain determined the subcellular localization of the formin as well as its protrusion activity between blebs and filopodia. We propose that isoform-selective actin assembly by DIAPH3 exerts specific and differentially regulated functions during cell adhesion and motility. |
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| Beschreibung: | Published: 20 December 2011 Gesehen am 20.09.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1748-7838 |
| DOI: | 10.1038/cr.2011.202 |