title: Dictyostelium chemotaxis: essential Ras activation and accessory signalling pathways for amplification.
abstract: Central to chemotaxis is the molecular mechanism by which cells exhibit directed movement in shallow gradients of a chemoattractant. We used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signalling module providing activation of Ras at the leading edge, which is sufficient for chemotaxis. The signalling enzymes PI3K, TorC2, PLA2 and sGC are not required for Ras activation and chemotaxis to folate or to steep gradients of cAMP, but they provide a memory of direction and improved orientation of the cell, which together increase the sensitivity about 150-fold for chemotaxis in shallow cAMP gradients.
authors.affiliation: Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Kortholt
authors.forename: Rama
authors.initials: R
authors.lastname: Kataria
authors.forename: Ineke
authors.initials: I
authors.lastname: Keizer-Gunnink
authors.forename: Wouter N
authors.initials: WN
authors.lastname: Van Egmond
authors.forename: Ankita
authors.initials: A
authors.lastname: Khanna
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005492:Folic Acid / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008954:Models, Biological; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D005492:Folic Acid; D000242:Cyclic AMP; D018631:ras Proteins
references.citation: Science. 2000 Feb 11;287(5455):1034-6
references.pmid: 10669414
references.citation: Mol Biol Cell. 2006 Oct;17(10):4543-50
references.pmid: 16885420
references.citation: J Cell Biol. 2004 Nov 8;167(3):505-18
references.pmid: 15534002
references.citation: Cell. 2002 May 31;109(5):611-23
references.pmid: 12062104
references.citation: Nat Rev Mol Cell Biol. 2004 Aug;5(8):626-34
references.pmid: 15366706
references.citation: J Cell Sci. 2008 Nov 1;121(Pt 21):3589-97
references.pmid: 18840645
references.citation: FEBS Lett. 1977 Jul 15;79(2):331-6
references.pmid: 196917
references.citation: Methods Mol Biol. 2009;571:473-88
references.pmid: 19763986
references.citation: Annu Rev Biophys. 2010;39:265-89
references.pmid: 20192768
references.citation: J Cell Biol. 2008 Feb 25;180(4):747-53
references.pmid: 18299345
references.citation: PLoS One. 2009 Aug 31;4(8):e6842
references.pmid: 19718261
references.citation: FEBS Lett. 1985 Jan 7;179(2):257-61
references.pmid: 3838158
references.citation: Science. 1981 Apr 24;212(4493):443-6
references.pmid: 6259734
references.citation: Curr Biol. 2007 May 1;17(9):813-7
references.pmid: 17462897
references.citation: J Cell Biol. 1995 Jun;129(6):1667-75
references.pmid: 7790362
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10566-70
references.pmid: 7937994
references.citation: Experientia. 1970 Apr 15;26(4):367-9
references.pmid: 4314777
references.citation: Curr Biol. 2008 Jul 22;18(14):1034-43
references.pmid: 18635356
references.citation: J Cell Sci. 2010 Mar 15;123(Pt 6):983-92
references.pmid: 20200230
references.citation: Mol Biol Cell. 2006 Sep;17(9):3921-9
references.pmid: 16790492
references.citation: Trends Cell Biol. 2004 Jun;14(6):303-11
references.pmid: 15183187
references.citation: Curr Biol. 2008 Oct 28;18(20):1587-1593
references.pmid: 18948008
references.citation: Cell Signal. 2008 Aug;20(8):1415-22
references.pmid: 18385017
references.citation: Dev Cell. 2007 Apr;12(4):603-14
references.pmid: 17419997
references.citation: Exp Cell Res. 1985 Oct;160(2):275-86
references.pmid: 2995097
references.citation: J Cell Biol. 1997 Oct 20;139(2):365-74
references.pmid: 9334341
references.citation: Proc Natl Acad Sci U S A. 1975 Dec;72(12):4991-3
references.pmid: 174088
references.citation: Exp Cell Res. 2005 May 15;306(1):47-55
references.pmid: 15878331
references.citation: J Cell Biol. 2007 Jun 4;177(5):809-16
references.pmid: 17535967