| First Author | Yayoshi-Yamamoto S | Year | 2000 |
| Journal | Mol Cell Biol | Volume | 20 |
| Issue | 18 | Pages | 6872-81 |
| PubMed ID | 10958683 | Mgi Jnum | J:64031 |
| Mgi Id | MGI:1888617 | Doi | 10.1128/mcb.20.18.6872-6881.2000 |
| Citation | Yayoshi-Yamamoto S, et al. (2000) FRL, a novel formin-related protein, binds to rac and regulates cell motility and survival of macrophages. Mol Cell Biol 20(18):6872-81 |
| abstractText | We have isolated a cDNA, frl (formin-related gene in leukocytes), a novel mammalian member of the formin gene family. The frl 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. |
