The neuron-specific formin Delphilin nucleates nonmuscle actin but does not enhance elongation

Mol Biol Cell. 2018 Mar 1;29(5):610-621. doi: 10.1091/mbc.E17-06-0363. Epub 2017 Dec 27.

Abstract

The formin Delphilin binds the glutamate receptor, GluRδ2, in dendritic spines of Purkinje cells. Both proteins play a role in learning. To understand how Delphilin functions in neurons, we studied the actin assembly properties of this formin. Formins have a conserved formin homology 2 domain, which nucleates and associates with the fast-growing end of actin filaments, influencing filament growth together with the formin homology 1 (FH1) domain. The strength of nucleation and elongation varies widely across formins. Additionally, most formins have conserved domains that regulate actin assembly through an intramolecular interaction. Delphilin is distinct from other formins in several ways: its expression is limited to Purkinje cells, it lacks classical autoinhibitory domains, and its FH1 domain has minimal proline-rich sequence. We found that Delphilin is an actin nucleator that does not accelerate elongation, although it binds to the barbed end of filaments. In addition, Delphilin exhibits a preference for actin isoforms, nucleating nonmuscle actin but not muscle actin, which has not been described or systematically studied in other formins. Finally, Delphilin is the first formin studied that is not regulated by intramolecular interactions. We speculate how the activity we observe is consistent with its localization in the small dendritic spines.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Animals
  • Cytoskeleton / metabolism
  • Dendritic Spines / metabolism*
  • Humans
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Protein Isoforms / metabolism
  • Purkinje Cells / metabolism
  • Receptors, Glutamate / metabolism

Substances

  • Actins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Receptors, Glutamate
  • delphilin
  • glutamate receptor delta 2