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Actin Binding Proteins

How Do Cells Build Lamellipodia?

Lamellipodia are specialized structures that cells construct to mediate protrusion, for example, during migration or phagocytosis. A great deal of evidence indicates that actin polymerization at the plasma membrane is the driving force for protrusion. Study of this process in numerous experimental system have identified key molecules involved in actin polymerization and organization, however, comprehensive analysis of these factors had never been performed in a single cell type. When plated on concanavalin A, S2 cells elaborate actin-based lamellae that resemble the leading edges of motile cells in terms of their structure, protein composition, and dynamics. We generated ~100 dsRNAs to inhibit genes known to regulate actin in Drosophila or in other systems and identified ~20 that produced aberrant cellular morphologies. Many of the morphological defects were consistent with predicted functions of the targets and these could be further categorized into functional pathways. However, our study also identified novel functions for several previously identified proteins in lamellipodia formation. Our analysis also revealed a novel regulatory mechanism for actin polymerization (by degradation of the Arp2/3 activator, SCAR) and also demonstrated the existence in vivo of an upstream regulatory pathway for SCAR activation (via Nck and Rac) (Rogers et al., 2003).


updated 4/9/07

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