My proposed research plan is directed at investigating how cells initiate and maintain filopodia. Filopodia arebiologically significant in many contexts, such as presentation of antigen by dendritic cells, metastatsis oftumors, and neuronal pathfinding. Therefore, this study will foster general interest. The study will examinethe regulatory molecule, fascin, and its role in the mechanism of filopodia formation. Preliminary dataindicate that fascin is necessary and sufficient for bundling of actin filaments in filopodia. Furthermore,photobleaching experiments reveal rapid recovery of GFP-fascin in filopodia in vivo. Structural and kineticanalysis of fascin and actin in filopodia suggest that filopodial bundles are maintained by dynamicassociation of fascin with actin-filaments. However, the molecular mechanism describing fascin recruitmentto filopodia remains elusive and, therefore, will be the subject of this proposal. The immediate goal of thisresearch plan is to identify the molecular basis for filopodia formation and breakdown, namely, therecruitment of fascin and coordination of actin polymerization, bundling, and depolymerization.
| Aratyn, Yvonne S; Schaus, Thomas E; Taylor, Edwin W et al. (2007) Intrinsic dynamic behavior of fascin in filopodia. Mol Biol Cell 18:3928-40 |
