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One research project explores the function of cytoplasmic motors, i.e. kinesins and dyneins, which carry cargoes along microtubules. We discovered these proteins many years ago, and have since been exploring how they work as machines, and how they organize traffic in the cell. This is important because motors orchestrate most cellular activities: cell division, axonal transport, cell morphogenesis, and even signal transduction. Our most recent studies are addressing the questions of how motors are linked to their cargoes and exactly what are these cargoes? These studies are telling us that motors are linked to vesicular cargo via soluble scaffolding proteins that have other functions in the cell, e.g. in scaffolding signal transduction pathways. The idea that motors localize pre-assembled signaling pathways has created a complicated new area for us to explore at the interface of signaling and molecular motors.
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The goal of this research project is to elucidate the biochemical mechanism of cytoplasmic mRNA localization. The transport of specific mRNAs to discrete subcellular domains is widespread, contributes to cell polarity, and is crucial for many activities that are of high interest, including the establishment of the body plan in the early embryo and synaptic plasticity in the brain. It seems remarkable that something this basic is still shrouded in mystery. To get at the molecular mechanisms, our research concentrates on a few RNAs that are localized to particular places in the oocytes of frogs and flies. We are deciphering the localization-directing signals in these RNAs, and biochemically isolating the cytoplasmic proteins with which these signals interact. Our studies have identified a highly conserved RNA binding protein, Vera/ZBP, which localizes diverse RNAs in different cellular contexts. We suspect this protein is a scaffold for a molecular motor. We are investigating the function of Vera/ZBP in flies and frogs, using biochemistry, genetics, and live cell imaging.
