Imaging sites of N-WASP activity in lamellipodia and invadopodia of carcinoma cells

Mike Lorenz, Hideki Yamaguchi, Yarong Wang, Robert H. Singer, John Condeelis

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


Cell migration is crucial for many biological and pathological processes such as chemotaxis of immune cells, fibroblast migration during wound healing, and tumor cell invasion and metastasis. Cells migrate forward by extending membrane protrusions. The formation of these protrusions is driven by assembly of actin filaments at the leading edge [1]. Neural Wiskott-Aldrich syndrome protein (N-WASP), a ubiquitous member of the WASP family, induces actin polymerization by activating Arp2/3 complex and is thought to regulate the formation of membrane protrusions [2, 3]. However, it is totally unclear how N-WASP activity is spatially and temporally regulated inside migrating cells. To detect and image sites of N-WASP activity during cell motility and invasion in carcinoma cells, we designed an N-WASP fluorescence resonance energy transfer (FRET) biosensor that distinguishes between the active and inactive conformations and mimics the function of endogenous N-WASP. Our data show that N-WASP is involved in lamellipodia extension, where it is activated at the leading edge, as well as in invadopodia formation of invasive carcinoma cells, where it is activated at the base. This is the first time that the activity of full-length N-WASP has been visualized in vivo, and this has lead to new insights for N-WASP function.

Original languageEnglish (US)
Pages (from-to)697-703
Number of pages7
JournalCurrent Biology
Issue number8
StatePublished - Apr 20 2004

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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