Queen pheromone modulates the expression of epigenetic modifier genes in the brain of honeybee workers

Pheromones are used by many insects to mediate social interactions. In the highly eusocial honeybee (Apis mellifera) queen mandibular pheromone (QMP) is involved in the regulation of reproduction and behaviour of workers. The molecular mechanisms by which QMP acts are largely unknown. Here we investigate how genes responsible for epigenetic modifications to DNA, RNA and histones respond to the presence of QMP. We show that several of these genes are upregulated in the honeybee brain when workers are exposed to QMP. This provides a plausible mechanism by which pheromone signalling may influence gene expression in the brain of honeybee workers. We propose that pheromonal communication systems, such as those used by social insects, evolved to respond to environmental signals by making use of existing epigenomic machineries.

Constitutively active RAS in S. pombe causes persistent Cdc42 signalling but only transient MAPK activation

The small GTPase RAS is a signalling hub for many pathways and oncogenic human RAS mutations are assumed to over-activate all of its downstream pathways. We tested this assumption in fission yeast, where, RAS-mediated pheromone signalling (PS) activates the MAPKSpk1 and Cdc42 pathways. Unexpectedly, we found that constitutively active Ras1.G17V induced immediate but only transient MAPKSpk1 activation, whilst Cdc42 activation persisted. Immediate but transient MAPKSpk1 activation was also seen in the deletion mutant of Cdc42-GEFScd1, a Cdc42 activator. We built a mathematical model using PS negative-feedback circuits and competition between the two Ras1 effectors, MAPKKKByr2 and Cdc42-GEFScd1. The model robustly predicted the MAPKSpk1 activation dynamics of an additional 21 PS mutants. Supporting the model, we showed that a recombinant Cdc42-GEFScd1 fragment competes with MAPKKKByr2 for Ras1 binding. Our study has established a concept that the constitutively active RAS propagates differently to downstream pathways where the system prevents MAPK overactivation.

Feedback inhibition of Ras activity coordinates cell fusion with cell-cell contact

In fission yeast Schizosaccharomyces pombe, pheromone signalling engages a GPCR-Ras-MAPK cascade to trigger sexual differentiation leading to gamete fusion. Cell-cell fusion necessitates local cell wall digestion, the location of which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signalling cascade. We constructed a live-reporter of active Ras1 (Ras1-GTP), also functional in S. cerevisiae, which revealed Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell-cell pairing, leading to cell lysis. Ras1 activity is restricted by the GTPase activating protein (GAP) Gap1, itself recruited to sites of Ras1-GTP. While the GAP domain on its own does not suffice for this localization, its recruitment to Ras1-GTP sites is essential to block untimely fusion attempts. We conclude that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell-cell engagement.

Rapid up- and down-regulation of pheromone signalling due to trail crowding in the ant Lasius niger

Social insects often respond to signals and cues from nest-mates, and these responses may include changes in the information they, in turn, transmit. During foraging, Lasius niger deposits a pheromone trail to recruit nestmates, and ants that experience trail crowding deposit pheromone less often. Less studied, however, is the time taken for signalling to revert to baseline levels after conditions have returned to baseline levels. In this paper we study the behaviour of L. niger foragers on a trail in which crowding is simulated by using dummy ants — black glass beads coated in nestmate cuticular hydrocarbons. Ants were allowed to make four repeat visits to a feeder with dummy ants, and thus crowding, being present on the trail on all visits (CCCC), none (UUUU) or only the first two (CCUU). If dummy ants were always present (CCCC), pheromone deposition probability was low in the first two visits (54% of ants deposited pheromone) and remained low in visits 3 and 4 (51%). If dummy ants were never present (UUUU) pheromone deposition probability was high in the first two visits (93%) and remained high in visits 3 and 4 (83%). If dummy ants were present on the first two visits but removed on the second two visits (CCUU) pheromone deposition probability was low in the first two visits (61%) but rose in the second two visits (69%). This demonstrates that even after pheromone deposition has been down-regulated due to crowding in the first two visits, it is rapidly up-regulated when crowding is reduced, although it does not immediately return to the base line level.

Who turned on the lights?: What the regulation of bacterial bioluminescence tells us about this and other bacterial group behaviours

Luminescence produced by organisms, or ‘bioluminescence’, holds a distinct fascination for humankind, and the study of bacterial bioluminescence has a long history in the field of microbiology. Advances in our understanding of bacterial bioluminescence have in many ways paralleled advances in the field as a whole. Intriguingly, studies of bioluminescent bacteria led to a seminal discovery in bacterial gene regulation and behaviour, because for bacteria, bioluminescence is a group activity. Bioluminescent bacteria communicate using pheromones, and as a result the regulatory decision to induce bioluminescence is only made if a group of bacteria has achieved a dense enough population to allow the build-up of pheromone. More recently, it has become clear that there are complex regulatory circuits governing not only luminescence, but also pheromone signalling itself. These additional layers of regulation pose new questions such as what are bacteria really saying to each other? Understanding regulation may also help answer ancient questions including, what use is luminescence?