Reference: Moseley JB, et al. (2004) A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol Biol Cell 15(2):896-907

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Abstract


Formins have conserved roles in cell polarity and cytokinesis and directly nucleate actin filament assembly through their FH2 domain. Here, we define the active region of the yeast formin Bni1 FH2 domain and show that it dimerizes. Mutations that disrupt dimerization abolish actin assembly activity, suggesting that dimers are the active state of FH2 domains. The Bni1 FH2 domain protects growing barbed ends of actin filaments from vast excesses of capping protein, suggesting that the dimer maintains a persistent association during elongation. This is not a species-specific mechanism, as the activities of purified mammalian formin mDia1 are identical to those of Bni1. Further, mDia1 partially complements BNI1 function in vivo, and expression of a dominant active mDia1 construct in yeast causes similar phenotypes to dominant active Bni1 constructs. In addition, we purified the Bni1-interacting half of the cell polarity factor Bud6 and found that it binds specifically to actin monomers and, like profilin, promotes rapid nucleotide exchange on actin. Bud6 and profilin show additive stimulatory effects on Bni1 activity and have a synthetic lethal genetic interaction in vivo. From these results, we propose a model in which Bni1 FH2 dimers nucleate and processively cap the elongating barbed end of the actin filament, and Bud6 and profilin generate a local flux of ATP-actin monomers to promote actin assembly.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
Moseley JB, Sagot I, Manning AL, Xu Y, Eck MJ, Pellman D, Goode BL
Primary Lit For
PFY1 | BUD6 | BNI1
Additional Lit For
ACT1

Gene Ontology Annotations 2 entries for 1 gene


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Gene/ComplexQualifierGene Ontology TermAnnotation ExtensionEvidenceSourceAssigned On
BUD6involved inpositive regulation of formin-nucleated actin cable assemblyIDASGD2013-08-07
BUD6involved inpositive regulation of formin-nucleated actin cable assemblyIGI with PFY1SGD2013-08-07
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Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 1 entry for 1 gene

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InteractorInteractorAssayAnnotationActionModification
BNI1BNI1Reconstituted Complexmanually curatedHit-BaitNo Modification
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