Regulation of actin network organization at cell-cell contacts.
Excitatory synapses of central nervous system (CNS) are specialized cell-cell contacts that mediate intercellular signal transmission from one neuron to another. The directional nature of signal requires synaptic contacts to be morphologically asymmetric with distinct protein components, while changes in synaptic communication during neural network formation require synapses to be plastic. Synapse morphology and plasticity require a dynamic actin cytoskeleton; however, the molecular mechanisms governing actin organization at the synapse are poorly understood. Cadherins are junctional proteins associated with the actin cytoskeleton that localize to synapses and regulate synaptic adhesion, stability and remodeling. The major intracellular components of cadherin junctions are the catenin proteins, and evidence suggests that cadherin–catenin complexes modulate an array of synaptic processes, including actin dynamics. A primary goal of the Kwiatkowski Lab is to understand how the cadherin-catenin complex organizes actin at cell-cell junctions, including synaptic contacts. We use a combination of protein biochemistry, cell biology, high-resolution microscopy and developmental biology to study actin dynamics at the molecular, cellular and organismal levels.
Kwiatkowski, A.V.*, Maiden, S.L.*, Pokutta, S., Choi, H.J., Nelson, W.J., Weis, W.I. and Hardin, J. In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans. Proc Natl Acad Sci USA 107, 14591-14596, 2010.
Benjamin, J.M.*, Kwiatkowski, A.V.*, Yang, C., Korobova, F., Pokutta, S., Svitkina, T., Weis, W.I. and Nelson, W.J. αE-Catenin regulates actin dynamics independently of cadherin-mediated cell-cell adhesion. J Cell Biol 189, 339-352, 2010. *Co-first author
Kwiatkowski, A.V., Garner, C.G., Nelson, W.J., and Gertler, F.B. Cell autonomous defects in cortical development revealed by two-color chimera analysis. Mol Cell Neurosci 41, 44 –50, 2009.
Dent, E. W., Kwiatkowski, A. V., Mebane, L., Philippar, U., Barzik, M., Rubinson, D. A., Furman, C., Burds, A. A., Alberts, A.S. and Gertler, F. B. Filopodia are required for cortical neurite formation. Nat Cell Biol 12, 1347-1359, 2007.
Kwiatkowski, A. V.*, Rubinson, D. A.*, Dent, E. W., van Veen, J. E., Leslie, J. D., Zhang, J., Mebane, L. M., Philippar, U., Pinheiro, E.M., Burds, A. A., Bronson, R. T., Mori, S., Fässler, R., and Gertler, F. B. Ena/VASP is required for neuritogenesis in the developing cortex. Neuron 56, 441-455, 2007. *Co-first author