A central requirement for eukaryotic cell growth and function is the ability to transport and sort proteins. Defects in protein trafficking can lead to debilitating diseases such as cystic fibrosis and Alzheimer's disease. Much of protein transport in a cell occurs via coated transport vesicles. My laboratory's research interests have focused on the molecular events involved in the formation of transport vesicles, and signal transduction that regulates the intracellular motility of transport vesicles along cytoskeletal filaments. We use the mammalian Golgi apparatus as a model system for these studies. Transport vesicles can be generated from Golgi membranes in cell-free reactions, allowing a biochemical dissection of this process.
A current focus of the laboratory is the role of transport vesicle coat proteins in cellular signaling. Binding interactions between vesicle coat proteins and signaling molecules regulate diverse processes in cells including vesicle motility, organelle positioning, cell growth, and apoptosis. Recent projects have examined vesicle-associated signal transduction that facilitates the entry of Shiga toxin, the toxin produced by pathogenic bacteria, into host cells. We have found that Shiga toxin induces changes to the cytoskeleton that subsequently facilitates its own entry into the host cell. A better understanding of this signaling process could ultimately provide insight into therapeutic strategies that could be used to treat E. coli infections.
1. Chen, J.L., Fucini, R.V., Lacomis, L., Erdjument-Bromage, H., Tempst, P., and Stamnes, M. (2005) Coatomer-bound Cdc42 regulates dynein recruitment to COPI vesicles. J. Cell Biol. 169, 383-389.
2. Xu, W.D. and Stamnes, M. (2006) The ADFH and charged/helical domains of drebrin and mAbp1 direct membrane binding and localization via distinct interactions with actin. J. Biol. Chem. 281, 11826-11833.
3. Hehnly, H., Sheff, D., and Stamnes, M. (2006) Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics. Mol. Biol. Cell 17, 4379-4389.
4. Hehnly, H. and Stamnes, M. (2007). Regulating cytoskeleton-based vesicle motility. FEBS lett. 581, 2112-2118.
5. Hehnly, H. Longhini, K., Chen J.L., Stamnes, M. (2009) Retrograde Shiga toxin trafficking is regulated by ARHGAP21 and Cdc42. Mol. Biol. Cell 20, 4303-4312.
6. Hehnly, H., Xu, W., Chen, J., and Stamnes, M. (2010) Cdc42 regulates microtubule-dependent Golgi positioning. Traffic 11, 1067-1078.