RRC ID 6550
Author Kato A, Kurita S, Hayashi A, Kaji N, Ohashi K, Mizuno K.
Title Critical roles of actin-interacting protein 1 in cytokinesis and chemotactic migration of mammalian cells.
Journal Biochem. J.
Abstract Cofilin regulates actin filament dynamics by stimulating actin filament disassembly and plays a critical role in cytokinesis and chemotactic migration. Aip1 (actin-interacting protein 1), also called WDR1 (WD-repeat protein 1), is a highly conserved WD-repeat protein in eukaryotes and promotes cofilin-mediated actin filament disassembly in vitro; however, little is known about the mechanisms by which Aip1 functions in cytokinesis and cell migration in mammalian cells. In the present study, we investigated the roles of Aip1 in cytokinesis and chemotactic migration of human cells by silencing the expression of Aip1 using siRNA (small interfering RNA). Knockdown of Aip1 in HeLa cells increased the percentage of multinucleate cells; this effect was reversed by expression of an active form of cofilin. In Aip1-knockdown cells, the cleavage furrow ingressed normally from anaphase to early telophase; however, an excessive accumulation of actin filaments was observed on the contractile ring in late telophase. These results suggest that Aip1 plays a crucial role in the completion of cytokinesis by promoting cofilin-mediated actin filament disassembly in telophase. We have also shown that Aip1 knockdown significantly suppressed chemokine-induced chemotactic migration of Jurkat T-lymphoma cells, and this was blocked by expression of an active form of cofilin. Whereas control cells mostly formed a single lamellipodium in response to chemokine stimulation, Aip1 knockdown cells abnormally exhibited multiple protrusions around the cells before and after cell stimulation. This indicates that Aip1 plays an important role in directional cell migration by restricting the stimulus-induced membrane protrusion to one direction via promoting cofilin activity.
Volume 414(2)
Pages 261-70
Published 2008-9-1
DOI 10.1042/BJ20071655
PII BJ20071655
PMID 18494608
MeSH Actin Depolymerizing Factors / genetics Actin Depolymerizing Factors / metabolism Actin Depolymerizing Factors / physiology Biological Transport / drug effects Cell Membrane / metabolism Cell Movement / drug effects Cell Movement / genetics Cell Movement / physiology* Cells, Cultured Chemokine CXCL12 / pharmacology Chemotaxis / drug effects Chemotaxis / genetics Chemotaxis / physiology Cytokinesis / drug effects Cytokinesis / genetics Cytokinesis / physiology* Cytoplasm / drug effects Cytoplasm / metabolism HeLa Cells Humans Jurkat Cells Microfilament Proteins / genetics Microfilament Proteins / metabolism Microfilament Proteins / physiology* Mitosis / drug effects Mitosis / genetics Mitosis / physiology
IF 3.857
Times Cited 28
Human and Animal Cells