FORMINS AND NATIVE COMPLEXES: REGULATION AND FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal is to understand how formin activities are regulated in vivo spatially and temporally. Given the potent effects formins have on actin assembly, they must be tightly controlled in the environment of a living cell. Our hypothesis is that through controlled local activation and attenuation of formins, their activities are harnessed to produce actin networks with highly specialized architectures and functions. What are these regulatory mechanisms? We are approaching this question using the model organism S. cerevisiae. The two S. cerevisiae formins Bni1 and Bnr1 assemble sets of highly dynamic actin cables, which in turn direct myosin-dependent polarized cell growth and morphogenesis. To elucidate the pathways controlling Bni1 and Bnr1 activities, we are using a set of affinity tags on known cell polarity factors and formin ligands to isolate the native protein complexes they form, and tandem mass spectrometry to identify the components of these complexes. In parallel, we are performing biochemical and genetic experiments to determine precisely how these proteins affect formin activities and contribute to cell polarity.