Leukocyte Chemotaxis



Contributors: Henry Bourne, Orion Weiner and Fei Wang
Artwork by: Gil R. Sambrano and Roger Sunahara
This map identifies links in signaling pathways that mediate chemotaxis of leukocytes. These pathways connect stimulation of G protein coupled chemokine receptors to regulation of the actin/myosin cytoskeleton. Many signal cascades converge on or are stimulated by PI(3,4,5)P3. This membrane lipid accumulates at the leading edge of neutrophils and appears to exert dual actions on Rho GTPases - that is, both as an upstream stimulator (probably of GEFs) and as a downstream mediator. One possibility is that this dual role is important for a positive feedback loop, centered on cell's the leading edge, that is responsible for conveying asymmetrical signals to the actin cytoskeleton, and therefore for morphologic polarity. The gradient of chemoattractant may bias the strength of this feedback loop toward the up-gradient edge of the cell.

Our criteria for assigning links to specific pathways was inclusive rather than exclusive. Consequently, some connections in the map are well established, while pathways are in many cases poorly defined. For investigators of B cells, one additional caution is in order: the links in this map are based for the most part on studies in neutrophils and T lymphocytes.

References:
Parent, C. A. and Devreotes, P. N. (1999). A cell's sense of direction. Science 284, 765-770.
Servant, G., Weiner, O. D., Herzmark, P., Balla, T., Sedat, J. W. and Bourne, H. R. (2000). Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287, 1037-1040.
Weiner, O. D., Servant, G., Parent, C. A., Devreotes, P. N. and Bourne, H. R. (2000). Cell polarity in response to chemoattractants. Chapter in Cell Polarity: Frontiers in Molecular Biology, D. G. Drubin, ed. (Oxford University Press).
Rickert, P., Weiner, O. D., Wang, F., Bourne, H.R., and Servant, G. (2000) Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends in Cell Biology, 10, 466-473.