Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation

• Verfasst von: Št̓astná, Jana [VerfasserIn]
• Verfasst von: Pan, Xiaoyu [VerfasserIn]
• Verfasst von: Kutscheidt, Stefan [VerfasserIn]
• Verfasst von: Lohmann, Volker [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Titel: Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation
• Verf.angabe: Jana Stastna, Xiaoyu Pan, Haicui Wang, Alina Kollmannsperger, Stefan Kutscheidt, Volker Lohmann, Robert Grosse, Oliver T. Fackler
• Jahr: 2012
• Jahr des Originals: 2011
• Umfang: 18 S.
• Teil: volume:22
• Teil: year:2012
• Teil: number:4
• Teil: pages:728-745
• Teil: extent:18
• Fussnoten: Published: 20 December 2011 ; Gesehen am 20.09.2018
• Titel Quelle: Enthalten in: Cell research
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 1990
• Jahr Quelle: 2012
• Band/Heft Quelle: 22(2012), 4, Seite 728-745
• ISSN Quelle: 1748-7838
• DOI: doi:10.1038/cr.2011.202
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581129033

Abstract

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.