ADF/cofilin promotes invadopodial membrane recycling during cell invasion in vivo

J Cell Biol. 2014 Mar 31;204(7):1209-18. doi: 10.1083/jcb.201312098. Epub 2014 Mar 24.

Abstract

Invadopodia are protrusive, F-actin-driven membrane structures that are thought to mediate basement membrane transmigration during development and tumor dissemination. An understanding of the mechanisms regulating invadopodia has been hindered by the difficulty of examining these dynamic structures in native environments. Using an RNAi screen and live-cell imaging of anchor cell (AC) invasion in Caenorhabditis elegans, we have identified UNC-60A (ADF/cofilin) as an essential regulator of invadopodia. UNC-60A localizes to AC invadopodia, and its loss resulted in a dramatic slowing of F-actin dynamics and an inability to breach basement membrane. Optical highlighting indicated that UNC-60A disassembles actin filaments at invadopodia. Surprisingly, loss of unc-60a led to the accumulation of invadopodial membrane and associated components within the endolysosomal compartment. Photobleaching experiments revealed that during normal invasion the invadopodial membrane undergoes rapid recycling through the endolysosome. Together, these results identify the invadopodial membrane as a specialized compartment whose recycling to form dynamic, functional invadopodia is dependent on localized F-actin disassembly by ADF/cofilin.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Basement Membrane / metabolism
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Movement*
  • Cell Polarity
  • Cell Surface Extensions / metabolism*
  • Endosomes / metabolism
  • Lysosomes / metabolism
  • Microfilament Proteins / physiology*
  • Microscopy, Fluorescence
  • Protein Multimerization
  • Protein Transport
  • Time-Lapse Imaging

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • Microfilament Proteins
  • UNC-60 protein, C elegans