Trends in Cell Biology
The formins: active scaffolds that remodel the cytoskeleton
Section snippets
Formin function
With all of the various cellular roles that formins have been shown to play, the common denominator is their profound influence over the actin cytoskeleton. In recent groundbreaking work, portions of the budding yeast formin Bni1p containing the FH1 and FH2 domains have been shown to directly nucleate actin to enhance the overall process of actin assembly 7, 27. Subsequent work on Bni1p, as well as on fission yeast Cdc12p, has provided further insights into the formin-induced actin nucleation 28
Molecular regulation of the formins
Numerous FH proteins (Drfs) have been identified in screens for Rho small GTPase effectors 17, 18, 20, 24, 34, 47. Rho GTPases act as binary molecular switches that cycle between an ‘on’ state when bound to GTP and an ‘off’ state after they hydrolyze GTP to GDP (see Fig. 4). The nucleotide status of the GTPase is governed by various GDP–GTP exchange factors (GEFs) that promote GDP release in response to extracellular stimuli and during the cell cycle [58]. Small GTPases regulate numerous cell
Formin-interacting proteins
Besides the Rho GTPases, there are many proteins that have been shown to interact with the formins that might participate in Drf signaling to actin, MTs or SRF. These binding partners might even be regulated by ‘activated’ Drfs. To date, however, none of the interactions with non-GTPase Drf-binding partners has been shown to be regulated. A list of Drf-binding partners is included in Fig. 4 and Table 1. Owing to the scope of the review, the discussion here will be limited mostly to mammalian
Concluding remarks
Numerous formin homology proteins have been found in variety of species, ranging from slime molds to humans. FH proteins play roles in cytokinesis, cell polarity, and recently they have been demonstrated to directly enhance actin nucleation in vitro. Most of what we know about formin molecular regulation has been learned from their characterization as effector proteins for activated Rho small GTPases. To date, it remains unknown whether the actin-nucleation activities associated with yeast
Acknowledgements
We are grateful to Jun Peng, Gregg Gundersen, Fred Chang, Harry Higgs, Tony Bretscher and Nick Duesbery for discussions and comments on the manuscript. We apologize to those whose work we have not discussed owing to space limitations or fell outside the scope of this review. A.S.A. is supported by Dept of Defense Breast Cancer Research Program Career Development Award (DAMD17–00–1-0190).
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