Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 6824K) PPT slides of all figures Supplemental Material Index Related biobytes podcast Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sarmiento, C. Articles by Condeelis, J. Search for Related Content PubMed PubMed Citation Articles by Sarmiento, C. Articles by Condeelis, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Substance via MeSH Medline Plus Health Information Cancer Related Collections Related In this Issue article Social Bookmarking                      What's this?

¹ Department of Anatomy and Structural Biology, ² Department of Pharmacology, and ³ Gruss Lipper Center for Biophotonics, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461
⁴ Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI 49503

Correspondence to Corina Sarmiento: csarmien{at}aecom.yu.edu

We examined the role of the actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion in response to epidermal growth factor (EGF), a key regulator in carcinoma cell invasion. We found that WAVE2 knockdown (KD) suppresses lamellipod formation and increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous KD of both proteins results in the formation of large jagged protrusions with lamellar properties and increased filopod formation. This suggests that another actin nucleation activity is at work in carcinoma cells in response to EGF. A mammalian Diaphanous–related formin, mDia1, localizes at the jagged protrusions in double KD cells. Constitutively active mDia1 recapitulated the phenotype, whereas inhibition of mDia1 blocked the formation of these protrusions. Increased RhoA activity, which stimulates mDia1 nucleation, was observed in the N-WASP/WAVE2 KD cells and was shown to be required for the N-WASP/WAVE2 KD phenotype. These data show that coordinate regulation between the WASP family and mDia proteins controls the balance between lamellar and lamellipodial protrusion activity.

Abbreviations used in this paper: Arp, actin-related protein; BE, barbed end; CRIB, Cdc42/Rac interactive binding domain; DN, dominant negative; FH2, formin homology 2; KD, knockdown; N-WASP, neural WASP; RBD, Rho binding domain; WASP, Wiskott-Aldrich syndrome protein.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related In this Issue article

Lamellipodia fight back formin

Nicole LeBrasseur
J. Cell Biol. 2008 180: 1052. [Full Text] [PDF]

This article has been cited by other articles:

• LeBrasseur, N. (2008). Lamellipodia fight back formin. JCB 180: 1052-1052 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents