Shaping Cells Using Modular Actin Filament Bundles

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Cell shape is a critical component of cell function. Cross-linked bundles of polarized actin filaments are common in eukaryotic cells and provide the scaffolding for creating and maintaining cell shape. Drosophila bristle cells are an excellent model system to investigate actin bundle assembly and cell shape control because they contain extraordinary large actin bundles and represent an extremely tractable system for genetic manipulation and live cell imaging. These bundles are an engineering marvel. They can grow to over 400 microns in length and taper 20-fold from 500 to 25 filaments - from base to tip. Amazingly, these structures are built by grafting together hundreds of 2-micron modules that first elongate and then thicken by filament addition. Bundle assembly is an unexpectedly dynamic process, and this project is aimed at determining how actin filament synthesis and turnover contributes to bundle assembly. Molecular and genetic tools will be employed to modify actin bundle assembly and confocal and electron microscopic techniques used to evaluate the biological consequences temporally and at high resolution. Results from this research should inform us about the construction of specialized membrane protrusions in many cells such as the microvilli on the adsorptive epithelial cells in the gut and the kidney and the stereocilia on the hair cells in the inner ear. This project will also incorporate undergraduates in a research-oriented team approach.