Mechanisms of eukaryotic gradient sensing
Chemotaxis, the cell’s ability to sense and migrate along shallow gradients of chemoattractant, plays an important role in the human immune system and many biological and physiological processes such as wound healing, embryogenesis and cancer metastasis (Carlos, 2001; Firtel and Chung, 2000; Muller et al., 2001; Thelen, 2001). Eukaryotic chemotactic cells, such as the slime mold Dictyostelium discoideum and human neutrophils, have the exquisite ability to sense and respond to shallow gradients of chemoattracant in the environment. The slime mold Dictyostelium discoideum provides a conveniently experimental model system for studying eukaryotic chemotaxis.
As a response to starvation Dictyostelium cells excrete the signaling molecule cAMP which acts as a chemoattractant for neighboring cells resulting in cellular aggregation and formation of a multicellular structure (Parent and Devreotes, 1996; Weijer, 2004). Recent experiments have demonstrated that an extracellular gradient of the Dictyostelium chemoattractant cAMP induces an intracellular gradient of several signaling proteins along the plasma membrane. In our lab, we explore the chemotactic response in single Dictyostelium cells by monitoring the localization dynamics of a key signaling protein in response to spatio-temporal gradients of chemoattractant.
Our Objective and Goals
- By quantitatively exploring cue-dependent cell polarization, we will better understand the molecular mechanism of directed cell motility (chemotaxis)
- By understanding stochastic cellular behavior, we will improve our understanding of non-genetic individuality and its impact on the fitness of a population
Dictyostelium discoideum: an experimental model system for eukaryotic Chemotaxis