Systematic analysis of the Myxococcus xanthus developmental gene regulatory network supports posttranslational regulation of FruA by C-signaling

Abstract

Upon starvation Myxococcus xanthus undergoes multicellular development. Rod-shaped cells move into mounds in which some cells differentiate into spores. Cells begin committing to sporulation at 24-30 h poststarvation, but the mechanisms governing commitment are unknown. FruA and MrpC are transcription factors that are necessary for commitment. They bind cooperatively to promoter regions and activate developmental gene transcription, including that of the dev operon. Leading up to and during the commitment period, dev mRNA increased in wild type, but not in a mutant defective in C-signaling, a short-range signaling interaction between cells that is also necessary for commitment. The C-signaling mutant exhibited [~]20-fold less dev mRNA than wild type at 30 h poststarvation, despite a similar level of MrpC and only twofold less FruA. Boosting the FruA level twofold in the C-signaling mutant had little effect on the dev mRNA level, and dev mRNA was not less stable in the C-signaling mutant. Neither did high cooperativity of MrpC and FruA binding upstream of the dev promoter explain the data. Rather, our systematic experimental and computational analyses support a model in which C-signaling activates FruA at least ninefold posttranslationally in order to commit a cell to spore formation.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=169 HEIGHT=200 SRC=\"FIGDIR/small/415331_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@c16410org.highwire.dtl.DTLVardef@909252org.highwire.dtl.DTLVardef@17668a8org.highwire.dtl.DTLVardef@d126c3_HPS_FORMAT_FIGEXP M_FIG C_FIG Abbreviated summaryStarvation promotes MrpC accumulation, whereas nutrients favor proteolysis. MrpC activates transcription of fruA, but FruA protein appears to be activated by short-range C-signaling in a cycle leading to mound formation and lysis of some cells. Activated FruA* and MrpC are proposed to cooperatively stimulate transcription of the dev operon and genes that commit starving rod-shaped cells to form spores, while Dev proteins slow commitment, resulting in a spore-filled fruiting body surrounded by peripheral rods.