The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Actin organization at cadherin mediated cell-cell contacts.

Cadherins are a family of cell-cell adhesion molecules necessary for the strong and specific cohesion of all solid tissues throughout the animal kingdom. Cadherins are essential for the mechanical stability of tissues, cell recognition, segregation of distinct tissues, and the rearrangement of sheets of interconnected cells that drive early embryogenesis. Cadherin function is actin dependent. However, we still do not understand how actin filaments are assembled and organized at cadherin mediated cell-cell contacts. We combine biochemical reconstitution with cell biology and imaging techniques to identify the molecular mechanisms necessary for organizing an actin cytoskeleton at cadherin dependent cell-cell junctions. Understanding these mechanisms will help us understand how adhesion and actin coordinate to help drive morphogenesis in developing organisms and how they act to maintain tissue structure in the adult organism.

Actin filament turnover dynamics.

Actin filaments in cells are highly dynamic, rapidly assembling in some regions of the cell while disassembling in others. While much is known about the molecular mechanism controlling actin polymerization, far less is known about actin depolymerization. Understanding depolymerization is important however as fast actin disassembly allows cells to rapidly reorganize their cytoskeleton in response to both internal and external cues. Cells express a number of proteins that help drive fast actin depolymerization. We use a combination of biochemistry, light microscopy, and electron microscopy to understand how each disassembly factor works alone and together to destabilize actin filaments. We use this information to understand how actin depolymerization helps determine both the structural and dynamical organization of different actin arrays in cells and how cells can maintain distinct actin arrays with varying stabilities.

Representative Publications

Normoyle KP, Brieher WM. Cyclase Associated Protein (CAP) Acts Directly on F-actin to Accelerate Cofilin-Mediated Actin Severing Across the Range of Physiological pH. J. Biol. Chem. In Press.

Tang VW, Brieher WM. 2012. α-Actinin-4/FSGS1 is required for Arp2/3-dependent actin assembly at the adherens junction. J Cell Biol. 196:115-30.

Kueh, H.Y., Charras, G.T., Mitchison, T.J., and Brieher, W.M. 2008. Actin filaments disassemble in abrupt bursts controlled by barbed-end regulators. J Cell Biol. 182:341-53.

Brieher, W.M., Kueh, H.Y., Ballif, B.A., and Mitchison, T.J. 2006. Rapid actin monomer–insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1. J. Cell Biol., 175:315–24.

Brieher, W.M., Coughlin, M., and Mitchison, T.J. 2004. Fascin-mediated propulsion of Listeria monocytogenes independent of frequent nucleation by the Arp2/3 complex. J. Cell. Biol., 165:233–42.

Complete Publications List