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

作　　者：Jana Stastna Xiaoyu Pan Haicui Wang Alina Kollmannsperger Stefan Kutscheidt Volker Lohmann Robert Grosse Oliver T Fackler 

机构地区：[1]Department of Infectious Diseases, Virology, University Hospital Heidelberg, INF 324, 69120 Heidelberg, Germany [2]Institute of Pharmacology, Biochemical Pharmacological Cente, University of Marburg, Karl-von-Frisch-Strasse 1, 35032 Marburg, Germany [3]Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, INF 345, 69120 Heidelberg, Germany

出　　处：《Cell Research》2012年第4期728-745,共18页细胞研究（英文版）

摘　　要：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 suhcellular 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 regu- lated functions during cell adhesion and motility.

关 键 词：actin remodeling diaphanous formins plasma membrane blebbing FILOPODIA cell adhesion 

分 类 号：Q946.1[生物学—植物学] Q959.117