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

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

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

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
Volume14
Issue number8
DOIs
StatePublished - Apr 20 2004

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Wiskott-Aldrich Syndrome Protein
pseudopodia
Pseudopodia
carcinoma
Cells
image analysis
Carcinoma
Imaging techniques
proteins
cells
Cell Movement
cell invasion
cell movement
Actins
Actin-Related Protein 2-3 Complex
Membranes
Biological Phenomena
Fluorescence Resonance Energy Transfer
Podosomes
biosensors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Imaging sites of N-WASP activity in lamellipodia and invadopodia of carcinoma cells. / Lorenz, Mike; Yamaguchi, Hideki; Wang, Yarong; Singer, Robert H.; Condeelis, John S.

In: Current Biology, Vol. 14, No. 8, 20.04.2004, p. 697-703.

Research output: Contribution to journalArticle

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