Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.
BACKGROUND
In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2) were originally identified as the factors (chlorinated alkylphenones) that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions.


RESULTS
To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase) and a decrease in the intracellular cGMP concentration ([cGMP](i)). DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase) and an increase in [cGMP](i). Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part.


CONCLUSIONS
Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules) for chemotaxis having differentiation-inducing activity.
Kuwayama
Hidekazu
H
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
Kubohara
Yuzuru
Y
D000818:Animals; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology*; D006588:Hexanones / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*
C490570:Differentiation-inducing factor-1, Dictyostelium; D006588:Hexanones; D006843:Hydrocarbons, Chlorinated; D000242:Cyclic AMP; D006152:Cyclic GMP
Biochim Biophys Acta. 2006 May;1760(5):754-61
16545913
Biochem J. 1988 Nov 15;256(1):23-8
3223901
Eur J Cell Biol. 2006 Sep;85(9-10):897-904
16962888
Development. 1998 Feb;125(4):691-9
9435289
Nucleic Acids Res. 2002 Jan 15;30(2):E2
11788728
Symp Soc Exp Biol. 1993;47:283-95
8165571
Proc Natl Acad Sci U S A. 1967 Sep;58(3):1152-4
4861307
FEBS Lett. 2008 Jun 18;582(14):2075-85
18452713
J Cell Biol. 2007 Jun 4;177(5):809-16
17535967
Dev Biol. 1982 May;91(1):191-6
6284569
Cell Differ. 1983 Dec;13(4):301-7
6687049
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15260-5
8986798
Development. 2006 Feb;133(3):439-48
16396914
Eur J Pharmacol. 1999 Sep 17;381(1):57-62
10528134
J Cell Sci. 2008 Mar 1;121(Pt 5):551-9
18287584
Biochem J. 1988 Feb 1;249(3):903-6
3355503
Development. 2006 Feb;133(3):449-58
16410410
Mol Biol Evol. 2002 Dec;19(12):2239-46
12446814
Nature. 1998 Apr 9;392(6676):565-8
9560152
Biochem Biophys Res Commun. 1999 Oct 5;263(3):790-6
10512759
Eur J Cell Biol. 2006 Sep;85(9-10):969-79
16814425
Mol Cell. 2000 Dec;6(6):1509-14
11163223
Mol Biol Cell. 2007 Dec;18(12):4772-9
17898079
Nature. 1976 Aug 19;262(5570):717-9
183142
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6749-54
12011437
Nature. 1987 Aug 27-Sep 2;328(6133):811-4
3627228
Cell. 2002 May 31;109(5):599-610
12062103
Cell. 2002 May 31;109(5):611-23
12062104
EMBO J. 2002 Sep 2;21(17):4560-70
12198158
J Cell Biol. 1993 Dec;123(6 Pt 1):1453-62
7902839
Proc Natl Acad Sci U S A. 1975 Aug;72(8):3163-6
171655
Curr Opin Immunol. 2000 Jun;12(3):336-41
10781407
Br Med Bull. 2000;56(4):985-1003
11359633
Development. 2004 Feb;131(3):513-23
14729573
Dev Cell. 2007 Apr;12(4):603-14
17419997
Mol Biol Cell. 2002 Nov;13(11):3878-89
12429832
EMBO Rep. 2004 Jan;5(1):35-40
14710184
Semin Cell Dev Biol. 1999 Dec;10(6):577-85
10706822
J Cell Biol. 2008 Feb 25;180(4):747-53
18299345
Cancer Res. 2004 Apr 1;64(7):2568-71
15059913
Dev Biol. 1990 Jul;140(1):189-95
2162792