Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells

J Cell Sci. 2006 Apr 15;119(Pt 8):1655-65. doi: 10.1242/jcs.02869. Epub 2006 Mar 28.

Abstract

The espin actin-bundling proteins, which are the target of deafness mutations, are present in the parallel actin bundles of stereocilia and microvilli and appear to increase their steady-state length. Here, we report a new activity of the espins, one that depends on their enigmatic WH2 domain: the ability to assemble a large actin bundle when targeted to a specific subcellular location. This activity was observed for wild-type espins targeted to the centrosome in transfected neuronal cells and for jerker espins targeted to the nucleolus in a wide variety of transfected cells as a result of the frameshifted peptide introduced into the espin C-terminus by the jerker deafness mutation. This activity, which appears specific to espins, requires two espin F-actin-binding sites and the actin-monomer-binding activity of the espin WH2 domain, but can be mimicked by adding a WH2 domain to an unrelated actin-bundling protein, villin. Espins do not activate the Arp2/3 complex in vitro, and bundle assembly is not indicative of in-vitro nucleation activity. Our results suggest a novel way to build actin bundles at specific sites in cells.

Publication types

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

MeSH terms

  • Actin-Related Protein 2-3 Complex / physiology
  • Actins / chemistry*
  • Amino Acid Sequence
  • Animals
  • Cell Nucleolus / metabolism
  • Centromere / metabolism*
  • LLC-PK1 Cells
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Neurons / metabolism*
  • PC12 Cells
  • Protein Isoforms / genetics*
  • Rats
  • Swine
  • Transfection

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • ESPN protein, human
  • Microfilament Proteins
  • Protein Isoforms