The role of formin tails in actin nucleation, processive elongation, and filament bundling

J Biol Chem. 2014 Oct 31;289(44):30602-30613. doi: 10.1074/jbc.M114.588368. Epub 2014 Sep 22.

Abstract

Formins are multidomain proteins that assemble actin in a wide variety of biological processes. They both nucleate and remain processively associated with growing filaments, in some cases accelerating filament growth. The well conserved formin homology 1 and 2 domains were originally thought to be solely responsible for these activities. Recently a role in nucleation was identified for the Diaphanous autoinhibitory domain (DAD), which is C-terminal to the formin homology 2 domain. The C-terminal tail of the Drosophila formin Cappuccino (Capu) is conserved among FMN formins but distinct from other formins. It does not have a DAD domain. Nevertheless, we find that Capu-tail plays a role in filament nucleation similar to that described for mDia1 and other formins. Building on this, replacement of Capu-tail with DADs from other formins tunes nucleation activity. Capu-tail has low-affinity interactions with both actin monomers and filaments. Removal of the tail reduces actin filament binding and bundling. Furthermore, when the tail is removed, we find that processivity is compromised. Despite decreased processivity, the elongation rate of filaments is unchanged. Again, replacement of Capu-tail with DADs from other formins tunes the processive association with the barbed end, indicating that this is a general role for formin tails. Our data show a role for the Capu-tail domain in assembling the actin cytoskeleton, largely mediated by electrostatic interactions. Because of its multifunctionality, the formin tail is a candidate for regulation by other proteins during cytoskeletal rearrangements.

Keywords: Actin; Capu; Cytoskeleton; Drosophila; Formin; Oocyte; TIRF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry*
  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster*
  • Kinetics
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / physiology*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Multimerization*
  • Protein Stability

Substances

  • Actins
  • Drosophila Proteins
  • Microfilament Proteins
  • capu protein, Drosophila