• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biophysjLink to Publisher's site
Biophys J. Jan 2002; 82(1 Pt 1): 50–63.
PMCID: PMC1302448

Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils.


Eukaryotic cells can detect shallow gradients of chemoattractants with exquisite precision and respond quickly to changes in the gradient steepness and direction. Here, we describe a set of models explaining both adaptation to uniform increases in chemoattractant and persistent signaling in response to gradients. We demonstrate that one of these models can be mapped directly onto the biochemical signal-transduction pathways underlying gradient sensing in amoebae and neutrophils. According to this scheme, a locally acting activator (PI3-kinase) and a globally acting inactivator (PTEN or a similar phosphatase) are coordinately controlled by the G-protein activation. This signaling system adapts perfectly to spatially homogeneous changes in the chemoattractant. In chemoattractant gradients, an imbalance between the action of the activator and the inactivator results in a spatially oriented persistent signaling, amplified by a substrate supply-based positive feedback acting through small G-proteins. The amplification is activated only in a continuous presence of the external signal gradient, thus providing the mechanism for sensitivity to gradient alterations. Finally, based on this mapping, we make predictions concerning the dynamics of signaling. We propose that the underlying principles of perfect adaptation and substrate supply-based positive feedback will be found in the sensory systems of other chemotactic cell types.

Full Text

The Full Text of this article is available as a PDF (200K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ali H, Richardson RM, Haribabu B, Snyderman R. Chemoattractant receptor cross-desensitization. J Biol Chem. 1999 Mar 5;274(10):6027–6030. [PubMed]
  • Alon U, Surette MG, Barkai N, Leibler S. Robustness in bacterial chemotaxis. Nature. 1999 Jan 14;397(6715):168–171. [PubMed]
  • Arkowitz RA. Responding to attraction: chemotaxis and chemotropism in Dictyostelium and yeast. Trends Cell Biol. 1999 Jan;9(1):20–27. [PubMed]
  • Barkai N, Leibler S. Robustness in simple biochemical networks. Nature. 1997 Jun 26;387(6636):913–917. [PubMed]
  • Blanchoin L, Pollard TD, Mullins RD. Interactions of ADF/cofilin, Arp2/3 complex, capping protein and profilin in remodeling of branched actin filament networks. Curr Biol. 2000 Oct 19;10(20):1273–1282. [PubMed]
  • Czech MP. PIP2 and PIP3: complex roles at the cell surface. Cell. 2000 Mar 17;100(6):603–606. [PubMed]
  • Eddy RJ, Pierini LM, Matsumura F, Maxfield FR. Ca2+-dependent myosin II activation is required for uropod retraction during neutrophil migration. J Cell Sci. 2000 Apr;113(Pt 7):1287–1298. [PubMed]
  • Gierer A, Meinhardt H. A theory of biological pattern formation. Kybernetik. 1972 Dec;12(1):30–39. [PubMed]
  • Goldbeter A, Koshland DE., Jr An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840–6844. [PMC free article] [PubMed]
  • Glogauer M, Hartwig J, Stossel T. Two pathways through Cdc42 couple the N-formyl receptor to actin nucleation in permeabilized human neutrophils. J Cell Biol. 2000 Aug 21;150(4):785–796. [PMC free article] [PubMed]
  • Janetopoulos C, Jin T, Devreotes P. Receptor-mediated activation of heterotrimeric G-proteins in living cells. Science. 2001 Mar 23;291(5512):2408–2411. [PubMed]
  • Jin T, Zhang N, Long Y, Parent CA, Devreotes PN. Localization of the G protein betagamma complex in living cells during chemotaxis. Science. 2000 Feb 11;287(5455):1034–1036. [PubMed]
  • Kim JY, Soede RD, Schaap P, Valkema R, Borleis JA, Van Haastert PJ, Devreotes PN, Hereld D. Phosphorylation of chemoattractant receptors is not essential for chemotaxis or termination of G-protein-mediated responses. J Biol Chem. 1997 Oct 24;272(43):27313–27318. [PubMed]
  • Knox BE, Devreotes PN, Goldbeter A, Segel LA. A molecular mechanism for sensory adaptation based on ligand-induced receptor modification. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2345–2349. [PMC free article] [PubMed]
  • Kobrinsky E, Mirshahi T, Zhang H, Jin T, Logothetis DE. Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization. Nat Cell Biol. 2000 Aug;2(8):507–514. [PubMed]
  • Loyet KM, Kowalchyk JA, Chaudhary A, Chen J, Prestwich GD, Martin TF. Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for regulated exocytosis. J Biol Chem. 1998 Apr 3;273(14):8337–8343. [PubMed]
  • Meinhardt H. Orientation of chemotactic cells and growth cones: models and mechanisms. J Cell Sci. 1999 Sep;112(Pt 17):2867–2874. [PubMed]
  • Missy K, Van Poucke V, Raynal P, Viala C, Mauco G, Plantavid M, Chap H, Payrastre B. Lipid products of phosphoinositide 3-kinase interact with Rac1 GTPase and stimulate GDP dissociation. J Biol Chem. 1998 Nov 13;273(46):30279–30286. [PubMed]
  • Neptune ER, Bourne HR. Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14489–14494. [PMC free article] [PubMed]
  • Oatey PB, Venkateswarlu K, Williams AG, Fletcher LM, Foulstone EJ, Cullen PJ, Tavaré JM. Confocal imaging of the subcellular distribution of phosphatidylinositol 3,4,5-trisphosphate in insulin- and PDGF-stimulated 3T3-L1 adipocytes. Biochem J. 1999 Dec 1;344(Pt 2):511–518. [PMC free article] [PubMed]
  • Parent CA, Devreotes PN. A cell's sense of direction. Science. 1999 Apr 30;284(5415):765–770. [PubMed]
  • Postma M, Van Haastert PJ. A diffusion-translocation model for gradient sensing by chemotactic cells. Biophys J. 2001 Sep;81(3):1314–1323. [PMC free article] [PubMed]
  • Pupillo M, Insall R, Pitt GS, Devreotes PN. Multiple cyclic AMP receptors are linked to adenylyl cyclase in Dictyostelium. Mol Biol Cell. 1992 Nov;3(11):1229–1234. [PMC free article] [PubMed]
  • Rickert P, Weiner OD, Wang F, Bourne HR, Servant G. Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends Cell Biol. 2000 Nov;10(11):466–473. [PMC free article] [PubMed]
  • Servant G, Weiner OD, Herzmark P, Balla T, Sedat JW, Bourne HR. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science. 2000 Feb 11;287(5455):1037–1040. [PMC free article] [PubMed]
  • Tall EG, Spector I, Pentyala SN, Bitter I, Rebecchi MJ. Dynamics of phosphatidylinositol 4,5-bisphosphate in actin-rich structures. Curr Biol. 2000 Jun 15;10(12):743–746. [PubMed]
  • Tang Y, Othmer HG. A G protein-based model of adaptation in Dictyostelium discoideum. Math Biosci. 1994 Mar;120(1):25–76. [PubMed]
  • Traynor D, Milne JL, Insall RH, Kay RR. Ca(2+) signalling is not required for chemotaxis in Dictyostelium. EMBO J. 2000 Sep 1;19(17):4846–4854. [PMC free article] [PubMed]
  • Van Duijn B, Van Haastert PJ. Independent control of locomotion and orientation during Dictyostelium discoideum chemotaxis. J Cell Sci. 1992 Aug;102(Pt 4):763–768. [PubMed]
  • Van Haastert PJ. Sensory adaptation of Dictyostelium discoideum cells to chemotactic signals. J Cell Biol. 1983 Jun;96(6):1559–1565. [PMC free article] [PubMed]
  • Vicker MG. Reaction-diffusion waves of actin filament polymerization/depolymerization in Dictyostelium pseudopodium extension and cell locomotion. Biophys Chem. 2000 Apr 14;84(2):87–98. [PubMed]
  • Wu D, Huang CK, Jiang H. Roles of phospholipid signaling in chemoattractant-induced responses. J Cell Sci. 2000 Sep;113(Pt 17):2935–2940. [PubMed]
  • Yi TM, Huang Y, Simon MI, Doyle J. Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4649–4653. [PMC free article] [PubMed]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...