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: Št̓astná, Jana (VerfasserIn) , Pan, Xiaoyu (VerfasserIn) , Kutscheidt, Stefan (VerfasserIn) , Lohmann, Volker (VerfasserIn) , Fackler, Oliver Till (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2012
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
Volltext
Verfasserangaben:Jana Stastna, Xiaoyu Pan, Haicui Wang, Alina Kollmannsperger, Stefan Kutscheidt, Volker Lohmann, Robert Grosse, Oliver T. Fackler

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520 |a 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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