PMID- 16545913 OWN - NLM STAT- MEDLINE DCOM- 20060705 LR - 20220129 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1760 IP - 5 DP - 2006 May TI - Identification of new differentiation inducing factors from Dictyostelium discoideum. PG - 754-61 AB - Developing Dictyostelium discoideum amoebae form a stalked fruiting body in which individual cells differentiate into either stalk cells or spores. The major known inducer of stalk cell differentiation is the chlorinated polyketide DIF-1 (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one); however a mutant blocked in the terminal step of DIF-1 biosynthesis still produces one of the prestalk cell subtypes - the pstA cells - as well as some mature stalk cells. We therefore searched for additional stalk cell-inducing factors in the medium supporting development of this mutant. These factors were purified by solvent extraction and HPLC and identified by mass spectroscopy and NMR. The mutant lacked detectable DIF-2 and DIF-3 (the pentanone and deschloro homologues of DIF-1) but four major stalk cell-inducing activities were detected, of which three were identified. Two compounds were predicted intermediates in DIF-1 biosynthesis: the desmethyl, and desmethyl-monochloro analogues of DIF-1 (dM-DIF-1 and Cl-THPH, respectively), supporting the previously proposed pathway of DIF-1 biosynthesis. The third compound was a novel factor and was identified as 4-methyl-5-pentylbenzene-1,3-diol (MPBD) with the structure confirmed by chemical synthesis. To investigate the potential roles of these compounds as signal molecules, their effects on morphological stalk and spore differentiation were examined in cell culture. All three induced morphological stalk cell differentiation. We found that synthetic MPBD also stimulated spore cell differentiation. Now that these factors are known to be produced and released during development, their biological roles can be pursued further. FAU - Saito, Tamao AU - Saito T AD - MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. tasaito@sci.hokudai.ac.jp FAU - Taylor, Graham W AU - Taylor GW FAU - Yang, Ji-Chun AU - Yang JC FAU - Neuhaus, David AU - Neuhaus D FAU - Stetsenko, Dmitry AU - Stetsenko D FAU - Kato, Atsushi AU - Kato A FAU - Kay, Robert R AU - Kay RR LA - eng GR - MC_U105115237/MRC_/Medical Research Council/United Kingdom GR - MC_U105178934/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060105 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (1-(3,5-dichloro-2,4,6-trihydroxyphenyl)hexane-1-one) RN - 0 (1-(3-chloro-2,4,6-trihydroxyphenyl)hexan-1-one) RN - 0 (4-methyl-5-pentylbenzene-1,3-diol) RN - 0 (Resorcinols) SB - IM MH - Animals MH - Cell Differentiation/drug effects MH - Chromatography, High Pressure Liquid MH - Dictyostelium/cytology/drug effects/*growth & development MH - Mass Spectrometry MH - Resorcinols/chemistry/isolation & purification/*pharmacology EDAT- 2006/03/21 09:00 MHDA- 2006/07/06 09:00 CRDT- 2006/03/21 09:00 PHST- 2005/09/12 00:00 [received] PHST- 2005/11/28 00:00 [revised] PHST- 2005/12/06 00:00 [accepted] PHST- 2006/03/21 09:00 [pubmed] PHST- 2006/07/06 09:00 [medline] PHST- 2006/03/21 09:00 [entrez] AID - S0304-4165(05)00392-2 [pii] AID - 10.1016/j.bbagen.2005.12.006 [doi] PST - ppublish SO - Biochim Biophys Acta. 2006 May;1760(5):754-61. doi: 10.1016/j.bbagen.2005.12.006. Epub 2006 Jan 5.