Competition and phylogeny determine community structure in Müllerian co-mimics.

Until recently, the study of negative and antagonistic interactions (for example, competition and predation) has dominated our understanding of community structure, maintenance and assembly. Nevertheless, a recent theoretical model suggests that positive interactions (for example, mutualisms) may counterbalance competition, facilitating long-term coexistence even among ecologically undifferentiated species. Müllerian mimics are mutualists that share the costs of predator education and are therefore ideally suited for the investigation of positive and negative interactions in community dynamics. The sole empirical test of this model in a Müllerian mimetic community supports the prediction that positive interactions outweigh the negative effects of spatial overlap (without quantifying resource acquisition). Understanding the role of trophic niche partitioning in facilitating the evolution and stability of Müllerian mimetic communities is now of critical importance, but has yet to be formally investigated. Here we show that resource partitioning and phylogeny determine community structure and outweigh the positive effects of Müllerian mimicry in a species-rich group of neotropical catfishes. From multiple, independent reproductively isolated allopatric communities displaying convergently evolved colour patterns, 92% consist of species that do not compete for resources. Significant differences in phylogenetically conserved traits (snout morphology and body size) were consistently linked to trait-specific resource acquisition. Thus, we report the first evidence, to our knowledge, that competition for trophic resources and phylogeny are pivotal factors in the stable evolution of Müllerian mimicry rings. More generally, our work demonstrates that competition for resources is likely to have a dominant role in the structuring of communities that are simultaneously subject to the effects of both positive and negative interactions.

The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter.

Pax6 transcription is under the control of two main promoters (P0 and P1), and these are autoregulated by Pax6. Additionally, Pax6 expression is under the control of the TGFbeta superfamily, although the precise mechanisms of such regulation are not understood. The effect of TGFbeta on Pax6 expression was studied in the FHL124 lens epithelial cell line and was found to cause up to a 50% reduction in Pax6 mRNA levels within 24 h. Analysis of luciferase reporters showed that Pax6 autoregulation of the P1 promoter, and its induction of a synthetic promoter encoding six paired domain-binding sites, were significantly repressed by both an activated TGFbeta receptor and TGFbeta ligand stimulation. Subsequently, a novel Pax6 binding site in P1 was shown to be necessary for autoregulation, indicating a direct influence of Pax6 protein on P1. In transfected cells, and endogenously in FHL124 cells, Pax6 co-immunoprecipitated with Smad3 following TGFbeta receptor activation, while in GST pull-down experiments, the MH1 domain of Smad3 was observed binding the RED sub-domain of the Pax6 paired domain. Finally, in DNA adsorption assays, activated Smad3 inhibited Pax6 from binding the consensus paired domain recognition sequence. We hypothesize that the Pax6 autoregulatory loop is targeted for repression by the TGFbeta/Smad pathway, and conclude that this involves diminished paired domain DNA-binding function resulting from a ligand-dependant interaction between Pax6 and Smad3.

The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling.

Disruption of components in the transforming growth factor-beta (TGF-beta) signalling cascade is a common occurrence in human cancers. TGF-beta pathway activation is accomplished via serine/threonine kinase receptors and intracellular Smad transcription factors. A key regulatory step involves specific ubiquitination by Smurfs that mediate the proteasomal degradation of Smads and/or receptors. Here, we report a novel interaction between Smads and ubiquitin C-terminal hydrolase UCH37, a deubiquitinating enzyme that could potentially reverse Smurf-mediated ubiquitination. In GST pull down experiments, UCH37 bound weakly to Smad2 and Smad3, and bound very strongly to Smad7 in a region that is distinct from the -PY- motif in Smad7 that interacts with Smurf ubiquitin ligases. Endogenous Smad7 and UCH37 formed a stable complex in U4A/JAK1 cells, and FLAG-Smad7 co-immunoprecipitated with HA-UCH37 in transfected HEK-293 cells. In addition, we show that UCH37 can deubiquitinate and stabilize the type I TGF-beta receptor. Furthermore, overexpression of UCH37 upregulates TGF-beta-dependent transcription, and this effect is reversed in cells subject to RNAi-mediated knockdown of endogenous UCH37. These findings support a new role for deubiquitinating enzymes in the control of the TGF-beta signalling pathway, and provide a novel molecular target for the design of inhibitors with therapeutic potential in cancer.