David Kast, Ph.D.

Assistant Professor
Cell Biology and Physiology

Molecular Cell Biology Program

  • 314 273-1852

  • 314-273-1854

  • 8228

  • 4900 South Building

  • kast@wustl.edu

  • cytoskeleton, membranes, intracellular trafficking, organelle biogenesis, fluorescence, crystallography

  • Understand fundamental cellular and molecular mechanisms that drive the biogenesis and dynamics of intracellular membrane compartments

Research Abstract:

The goal of the Kast lab is to understand fundamental cellular and molecular mechanisms that drive the biogenesis and dynamics of intracellular membrane compartments, including endocytic vesicles, the endoplasmic reticulum, the Golgi apparatus, and mitochondria. Cytoskeleton dynamics plays an essential role in the shaping and trafficking of these different membrane structures, however cannot remodel membranes directly. In order to harness the power of the cytoskeleton for the purpose of membrane shaping, cells use diverse sets of modular proteins that form protein complexes with cytoskeleton and signaling proteins, which in turn can partition membranes into autonomous membrane micro-domains. My lab is focused on (1) understanding fundamental molecular mechanisms that govern intracellular membrane reorganization and protein sorting; (2) stimulating the development of fluorescence based assays to delineate important signaling pathways involved in the biogenesis and trafficking vesicle; (3) defining the role(s) of endocytic dysfunction in cancer and neurological disease and take advantage of endocytic pathways to deliver next generation therapeutics to diseased cells. To accomplish these goals, the Kast lab employs a multifaceted approach that interleaves biochemical kinetics, fluorescence spectroscopy, x-ray crystallography, in vitro reconstitution, and live-cell imaging.

Selected Publications:

Kast D. J. and Dominguez R. (2017). The cytoskeleton-autophagy connection. Current Biology, 27:R318-R326.

Kast, D.J., Dominguez, R. (2015). WHAMM links actin assembly via the Arp2/3 complex to autophagy. Autophagy, 11:1702-1704

Kast, D. J., Zajac, A. L., Holzbaur, E. L., Ostap, E. M., and Dominguez R. (2015) WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism. Current Biology, 25:1791-1797.

Kast, D.J., Yang, C., Disanza, A., Boczkowska, M., Yadaiah, M., Scita, G., Svitkina, T, Dominguez, R. (2014). Molecular mechanism of IRSp53 regulation by autoinhibition and activation by Cdc42 and downstream effectors. Nature Structure and Molecular Biology, 21:413-422.

Boczkowska M, Rebowski G, Kast D. J., Dominguez R. (2014). Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs. Nat. Commun, 5:3308. DOI:10.1038/ncomms4308

Disanza, A., Bisi, S., Milanesi, F., Ushakov, D., Kast, D.J., Paola, M., Romet-Lemonne, Muller, HM., Nickel, W., Linkner, J., Waterschoot, D., Ampe, C., Cortellino, S., Dominguez, R., Carlier, MF., Faix, J., and Scita, G. (2013). CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering VASP through IRSp53. EMBO , 32:2735-50.

Turegun B, Kast D., Dominguez R (2013). Subunit Rtt102 controls the conformation of the Arp7/9 heterodimer and its interactions with nucleotide and the catalytic subunit of SWI/SNF remodelers. J Biol Chem, 288:35758-35768

Madasu Y, Suarez C, Kast D. J., Kovar DR and Dominguez R (2013). Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism. PNAS 110:E2677-E2686

Kast, D., Espinoza-Fonseca, L. M., Yi, C. and Thomas, D. D.. (2010). Phosphorylation induced structural changes in the smooth muscle myosin regulatory light chain. Proc Nat Acad Sci USA, 107:8207-8212.

Espinoza-Fonseca, L. M., Kast, D. and Thomas, D. D. (2008). Thermodynamic and structural basis of phosphorylation-induced disorder-to-order transition in the regulatory light chain of smooth muscle myosin. JACS, 130: 12208-12209.

Last Updated: 1/15/2018 10:57:11 AM

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