Taxonomic distribution of proteins containing Drf_GBD domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Drf_GBD domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals arole for Drf3 as an effector for Cdc42.

Peng J, Wallar BJ, Flanders A, Swiatek PJ, Alberts AS
Curr Biol. 2003; 13: 534-45

BACKGROUND: Mammalian Diaphanous-related formins (Drfs) act as Rho small GTPaseeffectors during growth factor-induced cytoskeletal remodeling and cell division.While both p140 mDia1 (herein called Drf1) and p134 mDia2 (Drf3) have been shown to bind in vitro to activated RhoA-C, and Drf3 has also been shown to bind toCdc42, little is known about the cellular function of these GTPase effectorpairs. Thus, we have begun targeting the murine Drf genes to address theirvarious contributions to small GTPase signaling in cytoskeletal remodeling anddevelopment. RESULTS: Drf1 +/+, +/-, and -/- cell lines were derived fromembryonic stem cells. While some Drf1 +/- lines had fewer actin stress fibers,several Drf1 +/- and -/- cells were more motile and had more abundant lamella andfilopodia. Because the apparent "gain-of-function" corresponded with elevatedlevels of Drf3 protein expression, we hypothesized that the effects on the actin cytoskeleton were due to Cdc42 utilization of Drf3 as an effector. In this study,we found that inactive Drf3 variants and microinjected Drf3 antibodies interferedwith Cdc42-induced filopodia. In addition, we observed that Drf3 contains apreviously unidentified CRIB-like motif within its GTPase binding domain (GBD).By fluorescent resonance energy transfer (FRET) analysis, we demonstrate thatthis motif is required for Cdc42 binding and Drf3 recruitment to the leading edgeand, surprisingly, to the microtubule organizing center (MTOC) of migratingfibroblasts. CONCLUSIONS: Our observations extend the role of the mammalian Drfs in cell signaling and demonstrate that Cdc42 not only activates Drf3, but guides the effector to sites at the cell cortex where it remodels the actincytoskeleton.