TY - JOUR
T1 - Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
AU - Seth, Abhinav
AU - Otomo, Chinatsu
AU - Rosen, Michael K.
PY - 2006/8/28
Y1 - 2006/8/28
N2 - Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor-mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function.
AB - Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor-mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function.
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U2 - 10.1083/jcb.200605006
DO - 10.1083/jcb.200605006
M3 - Article
C2 - 16943183
AN - SCOPUS:33748123994
SN - 0021-9525
VL - 174
SP - 701
EP - 713
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -