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- W4386506583 abstract "Formins are large, multidomain proteins that nucleate new actin filaments and accelerate elongation through a processive interaction with the barbed end of filaments. Their actin assembly activity is generally attributed to their eponymous Formin Homology (FH) 1 and 2 domains; however, evidence is mounting that regions outside of the FH1FH2 stretch also tune actin assembly. Here, we explore the underlying contributions of the tail domain, which spans the sequence between the FH2 domain and the C terminus of formins. Tails vary in length from ~0 to >200 residues and contain a number of recognizable motifs. The most well-studied motif is the ~15 residue long diaphanous autoregulatory domain (DAD). The DAD mediates all or nothing regulation of actin assembly through an intramolecular interaction with the diaphanous inhibitory domain (DID) in the N-terminal half of the protein. Multiple reports demonstrate that the tail can enhance both nucleation and processivity. In this study, we provide a high-resolution view of the alternative splicing encompassing the tail in the Formin Homology Domain-(Fhod) family of formins during development. While four distinct tails are predicted, we found significant levels of only two of these. We characterized the biochemical effects of the different tails. Surprisingly, the two highly expressed Fhodtails inhibit processive elongation and diminish the nucleation and elongation rates, while a third supports activity. These findings demonstrate a new mechanism of modulating actin assembly by formins and support the model that splice variants are specialized to build distinct actin structures during development." @default.
- W4386506583 created "2023-09-08" @default.
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- W4386506583 date "2023-09-06" @default.
- W4386506583 modified "2023-10-16" @default.
- W4386506583 title "Formin tails act as a switch, inhibiting or enhancing processive actin elongation" @default.
- W4386506583 doi "https://doi.org/10.1101/2023.09.06.556579" @default.
- W4386506583 hasPublicationYear "2023" @default.
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