QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 3 February 2004
doi: 10.1242/jcs.00921

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00921v1 117/6/837    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Biyasheva, A. Articles by Borisy, G. Search for Related Content PubMed PubMed Citation Articles by Biyasheva, A. Articles by Borisy, G. Pubmed/NCBI databases Protein Substance via MeSH

Cascade pathway of filopodia formation downstream of SCAR

¹ Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
² Ludwig Institute for Cancer Research, University College London Branch, London W1W 7BS, UK

^* Author for correspondence (e-mail: a-biyasheva{at}northwestern.edu)

Accepted 3 October 2003

The protrusion of two distinct actin-containing organelles, lamellipodia and filopodia, is thought to be regulated by two parallel pathways: from Rac1 through Scar/WAVEs to lamellipodia, and from Cdc42 through N-WASP to filopodia. We tested this hypothesis in Drosophila, which contains a single gene for each WASP subfamilies, SCAR and WASp. We performed targeted depletion of SCAR or WASp by dsRNA-mediated interference in two Drosophila cultured cell lines expressing lamellipodial and filopodial protrusion. Knockdown was verified by laser capture microdissection and RT-PCR, as well as western blotting. Morphometrical, kinetic and electron microscopy analyses of the SCAR-depleted phenotype in both cell types revealed strong inhibition of lamellipodial formation and cell spreading, as expected. More importantly, filopodia formation was also strongly inhibited, which is not consistent with the parallel pathway hypothesis. By contrast, depletion of WASp did not produce any significant phenotype, except for a slight inhibition of spreading, showing that both lamellipodia and filopodia in Drosophila cells are regulated predominantly by SCAR. We propose a new, cascade pathway model of filopodia regulation in which SCAR signals to lamellipodia and then filopodia arise from lamellipodia in response to additional signal(s).

Key words: Actin, SCAR, WASp, Lamellipodia, Filopodia, Drosophila cell lines, LCM

Related articles in JCS:

Actin model remodelled

JCS 2004 117: 602. [Full Text]