Eukaryotic chemotaxis is extremely complex. Cells can sense a wide range of stimuli, and many intracellular pathways are simultaneously involved. Recent genetic analyses of the steps between receptors and cytoskeleton, and how the cell controls actin and pseudopod behaviour, have yielded exciting new data but still no coherent understanding of chemotaxis. However, concentrating on pseudopods themselves and the physical processes that regulate them, rather than the internal signalling pathways, can simplify the data and help resolve the underlying mechanism. Direct action of electric fields and physical forces on cell migration suggest that mechanical forces and force-generating proteins like actin and myosin are centrally important in steering cells during chemotaxis.
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Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.
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