The F-BAR protein Hof1 tunes formin activity to sculpt actin cables during polarized growth.
Asymmetric cell growth and division rely on polarized actin cytoskeleton remodeling events, the regulation of which is poorly understood. In budding yeast, formins stimulate the assembly of an organized network of actin cables that direct polarized secretion. Here we show that the Fer/Cip4 homology-Bin amphiphysin Rvs protein Hof1, which has known roles in cytokinesis, also functions during polarized growth by directly controlling the activities of the formin Bnr1. A mutant lacking the C-terminal half of Hof1 displays misoriented and architecturally altered cables, along with impaired secretory vesicle traffic. In vitro, Hof1 inhibits the actin nucleation and elongation activities of Bnr1 without displacing the formin from filament ends. These effects depend on the Src homology 3 domain of Hof1, the formin homology 1 (FH1) domain of Bnr1, and Hof1 dimerization, suggesting a mechanism by which Hof1 "restrains" the otherwise flexible FH1-FH2 apparatus. In vivo, loss of inhibition does not alter actin levels in cables but, instead, cable shape and functionality. Thus Hof1 tunes formins to sculpt the actin cable network.
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Brian R
BR
Graziano
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Hoi-Ying E
HY
Yu
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Salvatore L
SL
Alioto
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Julian A
JA
Eskin
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Casey A
CA
Ydenberg
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
David P
DP
Waterman
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454.
Mikael
M
Garabedian
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454 goode@brandeis.edu.
Bruce L
BL
Goode
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D016764:Cell Polarity; D049109:Cell Proliferation; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D051304:Profilins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
D000199:Actins; C106463:BNR1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; C116847:HOF1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D051304:Profilins; D029701:Saccharomyces cerevisiae Proteins