Cell Biology

Changing Gears

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Science  15 Aug 2003:
Vol. 301, Issue 5635, pp. 896
DOI: 10.1126/science.301.5635.896b

Cells as unlike as the amoebae Dictyostelium and the neutrophil share the ability to propel themselves in response to chemoattractant gradients. This movement is achieved through coordinated polarization of intracellular signals that couple attractant detection with cytoskeletal activity. Previous studies have shown that signals at the leading edge of the neutrophil-like cell line HL-60 are regulated by a positive feedback loop initiated by trimeric G proteins. The production of phosphoinositide lipids and activation of the GTPase Rac leads to actin polymerization and pseudopod protrusion.

Xu et al. relate these front-end biochemical events to those regulating structurally distinct assemblies at the rear of migrating neutrophils, observing that leading-edge signals are countered by attractant desensitization at the sides and rear of HL-60 cells. These processes, which are also initiated by G proteins, activate the GTPase Rho and the Rho-dependent kinase ROCK, resulting in actin-myosin contraction and deadhesion of the trailing edge. Hence, activation of dialectical signaling pathways, even in the absence of a chemoattractant gradient, can establish functionally distinct front and rear domains. — SJS

Cell 114, 201 (2003).

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