Abstract
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.
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Selected References
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- Buczynski G., Grove B., Nomura A., Kleve M., Bush J., Firtel R. A., Cardelli J. Inactivation of two Dictyostelium discoideum genes, DdPIK1 and DdPIK2, encoding proteins related to mammalian phosphatidylinositide 3-kinases, results in defects in endocytosis, lysosome to postlysosome transport, and actin cytoskeleton organization. J Cell Biol. 1997 Mar 24;136(6):1271–1286. doi: 10.1083/jcb.136.6.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chung C. Y., Potikyan G., Firtel R. A. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol Cell. 2001 May;7(5):937–947. doi: 10.1016/s1097-2765(01)00247-7. [DOI] [PubMed] [Google Scholar]
- Devreotes P. Dictyostelium discoideum: a model system for cell-cell interactions in development. Science. 1989 Sep 8;245(4922):1054–1058. doi: 10.1126/science.2672337. [DOI] [PubMed] [Google Scholar]
- Firtel R. A., Meili R. Dictyostelium: a model for regulated cell movement during morphogenesis. Curr Opin Genet Dev. 2000 Aug;10(4):421–427. doi: 10.1016/s0959-437x(00)00107-6. [DOI] [PubMed] [Google Scholar]
- Meili R., Ellsworth C., Firtel R. A. A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium. Curr Biol. 2000 Jun 15;10(12):708–717. doi: 10.1016/s0960-9822(00)00536-4. [DOI] [PubMed] [Google Scholar]
- Meinhardt H. Orientation of chemotactic cells and growth cones: models and mechanisms. J Cell Sci. 1999 Sep;112(Pt 17):2867–2874. doi: 10.1242/jcs.112.17.2867. [DOI] [PubMed] [Google Scholar]
- Narang A., Subramanian K. K., Lauffenburger D. A. A mathematical model for chemoattractant gradient sensing based on receptor-regulated membrane phospholipid signaling dynamics. Ann Biomed Eng. 2001 Aug;29(8):677–691. doi: 10.1114/1.1385805. [DOI] [PubMed] [Google Scholar]
- Parent C. A., Blacklock B. J., Froehlich W. M., Murphy D. B., Devreotes P. N. G protein signaling events are activated at the leading edge of chemotactic cells. Cell. 1998 Oct 2;95(1):81–91. doi: 10.1016/s0092-8674(00)81784-5. [DOI] [PubMed] [Google Scholar]
- Parent C. A., Devreotes P. N. A cell's sense of direction. Science. 1999 Apr 30;284(5415):765–770. doi: 10.1126/science.284.5415.765. [DOI] [PubMed] [Google Scholar]
- Postma M., Van Haastert P. J. A diffusion-translocation model for gradient sensing by chemotactic cells. Biophys J. 2001 Sep;81(3):1314–1323. doi: 10.1016/S0006-3495(01)75788-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Potma E., de Boeij W. P., van Haastert P. J., Wiersma D. A. Real-time visualization of intracellular hydrodynamics in single living cells. Proc Natl Acad Sci U S A. 2001 Feb 6;98(4):1577–1582. doi: 10.1073/pnas.031575698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roelofs J., Meima M., Schaap P., Van Haastert P. J. The Dictyostelium homologue of mammalian soluble adenylyl cyclase encodes a guanylyl cyclase. EMBO J. 2001 Aug 15;20(16):4341–4348. doi: 10.1093/emboj/20.16.4341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Segall J. E. Behavioral responses of streamer F mutants of Dictyostelium discoideum: effects of cyclic GMP on cell motility. J Cell Sci. 1992 Mar;101(Pt 3):589–597. doi: 10.1242/jcs.101.3.589. [DOI] [PubMed] [Google Scholar]
- Servant G., Weiner O. D., Herzmark P., Balla T., Sedat J. W., Bourne H. R. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science. 2000 Feb 11;287(5455):1037–1040. doi: 10.1126/science.287.5455.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ueda M., Sako Y., Tanaka T., Devreotes P., Yanagida T. Single-molecule analysis of chemotactic signaling in Dictyostelium cells. Science. 2001 Oct 26;294(5543):864–867. doi: 10.1126/science.1063951. [DOI] [PubMed] [Google Scholar]
- Van Haastert P. J., Van der Heijden P. R. Excitation, adaptation, and deadaptation of the cAMP-mediated cGMP response in Dictyostelium discoideum. J Cell Biol. 1983 Feb;96(2):347–353. doi: 10.1083/jcb.96.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vicker M. G., Schill W., Drescher K. Chemoattraction and chemotaxis in Dictyostelium discoideum: myxamoeba cannot read spatial gradients of cyclic adenosine monophosphate. J Cell Biol. 1984 Jun;98(6):2204–2214. doi: 10.1083/jcb.98.6.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vicker M. G. The regulation of chemotaxis and chemokinesis in Dictyostelium amoebae by temporal signals and spatial gradients of cyclic AMP. J Cell Sci. 1994 Feb;107(Pt 2):659–667. doi: 10.1242/jcs.107.2.659. [DOI] [PubMed] [Google Scholar]
- Wurster B., Schubiger K., Wick U., Gerisch G. Cyclic GMP in Dictyostelium discoideum, Oscillations and pulses in response to folic acid and cyclic AMP signals. FEBS Lett. 1977 Apr 15;76(2):141–144. doi: 10.1016/0014-5793(77)80139-7. [DOI] [PubMed] [Google Scholar]
- van Es S., Devreotes P. N. Molecular basis of localized responses during chemotaxis in amoebae and leukocytes. Cell Mol Life Sci. 1999 Aug 15;55(10):1341–1351. doi: 10.1007/s000180050374. [DOI] [PMC free article] [PubMed] [Google Scholar]