Open AccessFRL, a Novel Formin-Related Protein, Binds to Rac and Regulates Cell Motility and Survival of Macrophages
Author(s) -
Shinri Yayoshi-Yamamoto,
Ichiro Taniuchi,
Takeshi Watanabe
Publication year - 2000
Publication title -
molecular and cellular biology (print)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.18.6872-6881.2000
Subject(s) - biology , formins , microbiology and biotechnology , actin cytoskeleton , rac gtp binding proteins , signal transduction , cell , cytoskeleton , rac1 , biochemistry
We have isolated a cDNA,frl (formin -related gene in leukocytes), a novel mammalian member of theformin gene family. Thefrl cDNA encodes a 160-kDa protein, FRL, that possesses FH1, FH2, and FH3 domains that are well conserved among other Formin-related proteins. An FRL protein is mainly localized in the cytosol and is highly expressed in spleen, lymph node, and bone marrow cells. Formin-related genes and proteins have been reported to play crucial roles in morphogenesis, cell polarity, and cytokinesis through interaction with Rho family small GTPases. FRL binds to Rac at its N-terminal region including the FH3 domain and associates with profilin at the FH1 domain. In a macrophage cell line, P388D1, overexpression of a truncated form of FRL containing only the FH3 domain (FH3-FRL) strongly inhibited cell adhesion to fibronectin and migration upon stimulation with a chemokine. Moreover, expression of the truncated FH3-FRL protein resulted in apoptotic cell death of P388D1 cells, suggesting that the truncated FH3-FRL protein may interfere with signals of FRL. Overexpression in the P388D1 cells of full-length FRL or of the truncated protein containing the FH3 and FH1 domains, with simultaneous expression of the truncated FH3-FRL protein, blocked apoptotic cell death and inhibition of cell adhesion and migration. These results suggest that FRL may play a role in the control of reorganization of the actin cytoskeleton in association with Rac and also in the regulation of the signal for cell survival.