Billions of white blood cells are streaming through your bloodstream. They’re on patrol, defending you from foreign invaders and protecting you from infection. Some respond to parasites, others to viruses and allergens. When certain white bloods cells called neutrophils detect an infection or area of injury, they will move in, engulfing and digesting any foreign bacteria or fungi in their path. But how does a neutrophil know where to go? How does it sense its target? What is its internal compass?
Neutrophils, and many other cells, use chemotaxis, the detection and directed movement of cells in response to a chemical gradient. In an advance publication of the Annual Review of Biophysics, Kristen Swaney and members of the Devreotes Lab in the Department of Cell Biology at Johns Hopkins University review the process of chemotaxis in eukaryotic cells (like our neutrophils). Much of what we know about chemotaxis in these cells is from the study of Dictyostelium, a soil-living amoeba commonly (and lovingly?) known as slime mold.
Neutrophil chasing a bacterium |
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The process of chemotaxis does not actually begin with signal detection but with random cell movement. Cells like neutrophils and Dictyostelium extend pseudopodia (literally “fake feet”) made up of filaments consisting of many molecules of actin protein. The actin in these filaments interacts with myosin protein at the cell’s end, causing contraction (just like in your muscle cells), propelling the cell forward. After extension, the cell reassembles the actin filaments, so it can begin again. With this ambling gait, the cell moves in a random direction. In the absence of an attractant, cells extend pseudopodia from each side uniformly. But once the cell senses an attractant, pseudopodia extend toward the signal. Most notable is the wave-like motion through the cell when an attractant is present. This wave is caused from the recruitment of actin-binding proteins sequentially from the inside of the cell to points on the surface and may underlie the generation of pseudopodia.
Cells detect chemical attractants with receptors on their surfaces. Once receptors bind an attractant molecule, a signal cascade is initiated and a network of signaling pathways is activated leading to the formation of actin into filaments and movement. Eukaryotic cells are capable of sensing both the amount of attractant and the location of the attractant in space, detecting how many receptors have bound attractant and where those receptors are located on their surface. Interestingly, if an attractant is present in low amounts, the cell will “adapt” to the presence of attractant and actually be more sensitive to an attractant gradient by ignoring the background.
Genetic analysis of Dictyostelium has revealed a complex and wide range of interacting players in the process of chemotaxis. In her review, Swaney emphasizes that we still have much to learn about the components involved in wave propagation, the mechanism of attractant adaptation, the localization of components, and the complexity of multiple signaling networks. There are many pieces to an internal compass.
2011…
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