A cell's sense of direction

Science

Volumn 284, Issue 5415, 1999, Pages 765-769

  Parent, Carole A ^a   Devreotes, Peter N ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; CHEMOATTRACTANT; GUANINE NUCLEOTIDE BINDING PROTEIN; PLECKSTRIN; PROTEIN SUBUNIT; RECEPTOR PROTEIN;

CELL FUNCTION; CHEMOTAXIS; CYTOSKELETON; DICTYOSTELIUM DISCOIDEUM; EUKARYOTE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; RECEPTOR DENSITY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL MEMBRANE; CHEMOTACTIC FACTORS; CHEMOTAXIS; CHEMOTAXIS, LEUKOCYTE; DICTYOSTELIUM; GTP-BINDING PROTEINS; HUMANS; LEUKOCYTES; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 0033617576     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.284.5415.765     Document Type: Review

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57. i with Pertussis toxin [C. Gerard and N. P. Gerard, Curr. Opin. Immunol. 6, 140 (1994); M. Baggiolini, Nature 392, 565 (1998)]. Knockouts of CXCR2 and CCR2 are chemotactically insensitive to specific chemokines, and expression of specific receptors in tissue culture cells confers chemotactic sensitivity to the appropriate chemokines [G. Cacalano et al., Science 265, 682 (1994); J. J. Campbell, S. Quin, K. B. Bacon, C. R. Mackay, E. C. Butcher, J. Cell Biol. 134, 255 (1996); L. Boring et al., J. Clin. Invest. 100, 2552 (1997)].
58. i with Pertussis toxin [C. Gerard and N. P. Gerard, Curr. Opin. Immunol. 6, 140 (1994); M. Baggiolini, Nature 392, 565 (1998)]. Knockouts of CXCR2 and CCR2 are chemotactically insensitive to specific chemokines, and expression of specific receptors in tissue culture cells confers chemotactic sensitivity to the appropriate chemokines [G. Cacalano et al., Science 265, 682 (1994); J. J. Campbell, S. Quin, K. B. Bacon, C. R. Mackay, E. C. Butcher, J. Cell Biol. 134, 255 (1996); L. Boring et al., J. Clin. Invest. 100, 2552 (1997)].
59. i with Pertussis toxin [C. Gerard and N. P. Gerard, Curr. Opin. Immunol. 6, 140 (1994); M. Baggiolini, Nature 392, 565 (1998)]. Knockouts of CXCR2 and CCR2 are chemotactically insensitive to specific chemokines, and expression of specific receptors in tissue culture cells confers chemotactic sensitivity to the appropriate chemokines [G. Cacalano et al., Science 265, 682 (1994); J. J. Campbell, S. Quin, K. B. Bacon, C. R. Mackay, E. C. Butcher, J. Cell Biol. 134, 255 (1996); L. Boring et al., J. Clin. Invest. 100, 2552 (1997)].
60. i with Pertussis toxin [C. Gerard and N. P. Gerard, Curr. Opin. Immunol. 6, 140 (1994); M. Baggiolini, Nature 392, 565 (1998)]. Knockouts of CXCR2 and CCR2 are chemotactically insensitive to specific chemokines, and expression of specific receptors in tissue culture cells confers chemotactic sensitivity to the appropriate chemokines [G. Cacalano et al., Science 265, 682 (1994); J. J. Campbell, S. Quin, K. B. Bacon, C. R. Mackay, E. C. Butcher, J. Cell Biol. 134, 255 (1996); L. Boring et al., J. Clin. Invest. 100, 2552 (1997)].
61. i with Pertussis toxin [C. Gerard and N. P. Gerard, Curr. Opin. Immunol. 6, 140 (1994); M. Baggiolini, Nature 392, 565 (1998)]. Knockouts of CXCR2 and CCR2 are chemotactically insensitive to specific chemokines, and expression of specific receptors in tissue culture cells confers chemotactic sensitivity to the appropriate chemokines [G. Cacalano et al., Science 265, 682 (1994); J. J. Campbell, S. Quin, K. B. Bacon, C. R. Mackay, E. C. Butcher, J. Cell Biol. 134, 255 (1996); L. Boring et al., J. Clin. Invest. 100, 2552 (1997)].
62. Directional sensing is believed to be mediated by the βγ subunits of G proteins because overexpression of βγ-sequestering proteins in a lymphocyte cell line or human embryonic kidney (HEK) 293 cells inhibits movement toward chemoattractant [H. Arai, C. L. Tsou, I. F. Charo, Proc. Natl. Acad. Sci. U.S.A. 94, 14495 (1997); E. R. Neptune and H. R. Bourne, ibid., p. 14489]. In addition, specific alleles in the D. discoideum β subunit lead to weak chemotaxis toward cAMP [J. Tian, M. Amzel, P. N. Devreotes, L. Wu, Mol. Biol. Cell 9, 2949 (1998)]. In yeast, Cdc24 and Gβγ subunits form a complex, and specific alleles in either component that inhibit their association show defects in directed growth (chemotropism) [A. Nern and R. A. Arkowitz, Nature 391, 195 (1998)]. The kinetics of these responses vary, peaking within a few seconds to 1 min after the addition of chemoattractants. In some cases, such as in actin polymerization, there is one peak after a few seconds and a second one after 90 s [J. Condeelis et al., Cell Motil. Cytostel. 10, 77 (1988)].
63. Directional sensing is believed to be mediated by the βγ subunits of G proteins because overexpression of βγ-sequestering proteins in a lymphocyte cell line or human embryonic kidney (HEK) 293 cells inhibits movement toward chemoattractant [H. Arai, C. L. Tsou, I. F. Charo, Proc. Natl. Acad. Sci. U.S.A. 94, 14495 (1997); E. R. Neptune and H. R. Bourne, ibid., p. 14489]. In addition, specific alleles in the D. discoideum β subunit lead to weak chemotaxis toward cAMP [J. Tian, M. Amzel, P. N. Devreotes, L. Wu, Mol. Biol. Cell 9, 2949 (1998)]. In yeast, Cdc24 and Gβγ subunits form a complex, and specific alleles in either component that inhibit their association show defects in directed growth (chemotropism) [A. Nern and R. A. Arkowitz, Nature 391, 195 (1998)]. The kinetics of these responses vary, peaking within a few seconds to 1 min after the addition of chemoattractants. In some cases, such as in actin polymerization, there is one peak after a few seconds and a second one after 90 s [J. Condeelis et al., Cell Motil. Cytostel. 10, 77 (1988)].
64. Directional sensing is believed to be mediated by the βγ subunits of G proteins because overexpression of βγ-sequestering proteins in a lymphocyte cell line or human embryonic kidney (HEK) 293 cells inhibits movement toward chemoattractant [H. Arai, C. L. Tsou, I. F. Charo, Proc. Natl. Acad. Sci. U.S.A. 94, 14495 (1997); E. R. Neptune and H. R. Bourne, ibid., p. 14489]. In addition, specific alleles in the D. discoideum β subunit lead to weak chemotaxis toward cAMP [J. Tian, M. Amzel, P. N. Devreotes, L. Wu, Mol. Biol. Cell 9, 2949 (1998)]. In yeast, Cdc24 and Gβγ subunits form a complex, and specific alleles in either component that inhibit their association show defects in directed growth (chemotropism) [A. Nern and R. A. Arkowitz, Nature 391, 195 (1998)]. The kinetics of these responses vary, peaking within a few seconds to 1 min after the addition of chemoattractants. In some cases, such as in actin polymerization, there is one peak after a few seconds and a second one after 90 s [J. Condeelis et al., Cell Motil. Cytostel. 10, 77 (1988)].
65. Directional sensing is believed to be mediated by the βγ subunits of G proteins because overexpression of βγ-sequestering proteins in a lymphocyte cell line or human embryonic kidney (HEK) 293 cells inhibits movement toward chemoattractant [H. Arai, C. L. Tsou, I. F. Charo, Proc. Natl. Acad. Sci. U.S.A. 94, 14495 (1997); E. R. Neptune and H. R. Bourne, ibid., p. 14489]. In addition, specific alleles in the D. discoideum β subunit lead to weak chemotaxis toward cAMP [J. Tian, M. Amzel, P. N. Devreotes, L. Wu, Mol. Biol. Cell 9, 2949 (1998)]. In yeast, Cdc24 and Gβγ subunits form a complex, and specific alleles in either component that inhibit their association show defects in directed growth (chemotropism) [A. Nern and R. A. Arkowitz, Nature 391, 195 (1998)]. The kinetics of these responses vary, peaking within a few seconds to 1 min after the addition of chemoattractants. In some cases, such as in actin polymerization, there is one peak after a few seconds and a second one after 90 s [J. Condeelis et al., Cell Motil. Cytostel. 10, 77 (1988)].
66. Directional sensing is believed to be mediated by the βγ subunits of G proteins because overexpression of βγ-sequestering proteins in a lymphocyte cell line or human embryonic kidney (HEK) 293 cells inhibits movement toward chemoattractant [H. Arai, C. L. Tsou, I. F. Charo, Proc. Natl. Acad. Sci. U.S.A. 94, 14495 (1997); E. R. Neptune and H. R. Bourne, ibid., p. 14489]. In addition, specific alleles in the D. discoideum β subunit lead to weak chemotaxis toward cAMP [J. Tian, M. Amzel, P. N. Devreotes, L. Wu, Mol. Biol. Cell 9, 2949 (1998)]. In yeast, Cdc24 and Gβγ subunits form a complex, and specific alleles in either component that inhibit their association show defects in directed growth (chemotropism) [A. Nern and R. A. Arkowitz, Nature 391, 195 (1998)]. The kinetics of these responses vary, peaking within a few seconds to 1 min after the addition of chemoattractants. In some cases, such as in actin polymerization, there is one peak after a few seconds and a second one after 90 s [J. Condeelis et al., Cell Motil. Cytostel. 10, 77 (1988)].
67. The mechanisms for inhibition of all of the responses are not known. Candidates include the GTPase activity of G proteins, in conjunction with RGS proteins, and receptor-desensitization mechanisms. Several studies have shown that receptor phosphorytation on the COOH-terminus is associated with decreases in receptor affinity and receptor internalization. Cells expressing tailless CCR2B, fMLP, or cAR1 receptors or cAR1 receptors where all of the serines in the COOH-terminal domain were substituted with alanine residues show altered desensitization responses (decrease in affinity, internalization) but are still able to carry out chemotaxis [H. Arai, F. S. Monteclaro, C. L. Tsou, C. Franci, I. F. Charo, J. Biol. Chem. 272, 25037 (1997); M. H. Hsu, S. C. Chiang, R. D. Ye, E. R. Prossnitz, ibid., p. 29426; J. Y. Kim et al., ibid., p. 27313].
68. The mechanisms for inhibition of all of the responses are not known. Candidates include the GTPase activity of G proteins, in conjunction with RGS proteins, and receptor-desensitization mechanisms. Several studies have shown that receptor phosphorytation on the COOH-terminus is associated with decreases in receptor affinity and receptor internalization. Cells expressing tailless CCR2B, fMLP, or cAR1 receptors or cAR1 receptors where all of the serines in the COOH-terminal domain were substituted with alanine residues show altered desensitization responses (decrease in affinity, internalization) but are still able to carry out chemotaxis [H. Arai, F. S. Monteclaro, C. L. Tsou, C. Franci, I. F. Charo, J. Biol. Chem. 272, 25037 (1997); M. H. Hsu, S. C. Chiang, R. D. Ye, E. R. Prossnitz, ibid., p. 29426; J. Y. Kim et al., ibid., p. 27313].
69. The mechanisms for inhibition of all of the responses are not known. Candidates include the GTPase activity of G proteins, in conjunction with RGS proteins, and receptor-desensitization mechanisms. Several studies have shown that receptor phosphorytation on the COOH-terminus is associated with decreases in receptor affinity and receptor internalization. Cells expressing tailless CCR2B, fMLP, or cAR1 receptors or cAR1 receptors where all of the serines in the COOH-terminal domain were substituted with alanine residues show altered desensitization responses (decrease in affinity, internalization) but are still able to carry out chemotaxis [H. Arai, F. S. Monteclaro, C. L. Tsou, C. Franci, I. F. Charo, J. Biol. Chem. 272, 25037 (1997); M. H. Hsu, S. C. Chiang, R. D. Ye, E. R. Prossnitz, ibid., p. 29426; J. Y. Kim et al., ibid., p. 27313].
70. Supplemental Web material is available at www. sciencemag.org/feature/data/990801.shl.
71. G. Servant, O. D. Weiner, E. R. Neptune, J. W. Sedat, H. R. Bourne, Mol. Biol. Cell 10, 1163 (1999).
72. We thank S. van Es and J. Silverman for their excellent comments and stimulating discussions; G. Servant, O. D. Weiner, and H. R. Bourne for providing panel B of Fig. 2; and R. A. Firtel for panel C of Fig. 4. Supported by NIH grant GM57874 and GM28007.