Espin cross-links cause the elongation of microvillus-type parallel actin bundles in vivo

J Cell Biol. 2003 Dec 8;163(5):1045-55. doi: 10.1083/jcb.200309093. Epub 2003 Dec 1.

Abstract

The espin actin-bundling proteins, which are the target of the jerker deafness mutation, caused a dramatic, concentration-dependent lengthening of LLC-PK1-CL4 cell microvilli and their parallel actin bundles. Espin level was also positively correlated with stereocilium length in hair cells. Villin, but not fascin or fimbrin, also produced noticeable lengthening. The espin COOH-terminal peptide, which contains the actin-bundling module, was necessary and sufficient for lengthening. Lengthening was blocked by 100 nM cytochalasin D. Espin cross-links slowed actin depolymerization in vitro less than twofold. Elimination of an actin monomer-binding WASP homology 2 domain and a profilin-binding proline-rich domain from espin did not decrease lengthening, but made it possible to demonstrate that actin incorporation was restricted to the microvillar tip and that bundles continued to undergo actin treadmilling at approximately 1.5 s-1 during and after lengthening. Thus, through relatively subtle effects on actin polymerization/depolymerization reactions in a treadmilling parallel actin bundle, espin cross-links cause pronounced barbed-end elongation and, thereby, make a longer bundle without joining shorter modules.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Binding Sites
  • Carrier Proteins / metabolism
  • Cell Line
  • Contractile Proteins*
  • Cytochalasin D / metabolism
  • Fluorescence Recovery After Photobleaching
  • Hair Cells, Auditory / cytology
  • Hair Cells, Auditory / metabolism
  • Humans
  • Membrane Glycoproteins / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microvilli / metabolism*
  • Microvilli / ultrastructure
  • Nucleic Acid Synthesis Inhibitors / metabolism
  • Profilins
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Swine

Substances

  • Actins
  • Carrier Proteins
  • Contractile Proteins
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Nucleic Acid Synthesis Inhibitors
  • PFN1 protein, human
  • Profilins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • espin protein, mouse
  • plastin
  • villin
  • fascin
  • Cytochalasin D