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Biophys J, September 2002, p. 1361-1367, Vol. 83, No. 3

Establishing Direction during Chemotaxis in Eukaryotic Cells

Wouter-Jan Rappel,* Peter J. Thomas,dagger Herbert Levine,* and William F. LoomisDagger

 *Department of Physics, University of California, San Diego, La Jolla, California 92093-0319,  dagger Computational Neurobiology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186-5800, and  Dagger Division of Biology, University of California, San Diego, La Jolla, California 92093-0368 USA

Several recent studies have demonstrated that eukaryotic cells, including amoeboid cells of Dictyostelium discoideum and neutrophils, respond to chemoattractants by translocation of PH-domain proteins to the cell membrane, where these proteins participate in the modulation of the cytoskeleton and relay of the signal. When the chemoattractant is released from a pipette, the localization is found predominantly on the proximal side of the cell. The recruitment of PH-domain proteins, particularly for Dictyostelium cells, occurs very rapidly (<2 s). Thus, the mechanism responsible for the first step in the directional sensing process of a cell must be able to establish an asymmetry on the same time scale. Here, we propose a simple mechanism in which a second messenger, generated by local activation of the membrane, diffuses through the interior of the cell, suppresses the activation of the back of the cell, and converts the temporal gradient into an initial cellular asymmetry. Numerical simulations show that such a mechanism is plausible. Available evidence suggests that the internal inhibitor may be cGMP, which accumulates within less than a second following treatment of cells with external cAMP.

Biophys J, September 2002, p. 1361-1367, Vol. 83, No. 3
© 2002 by the Biophysical Society   0006-3495/02/09/1361/07  $2.00


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