Ménage à trois: Aldosterone,sodium and nitric oxide in vascular endothelium

Aldosterone, a mineralocorticoid hormone mainly synthesized in the adrenal cortex, has been recognized to be a regulator of cell mechanics. Recent data from a number of laboratories implicate that, besides kidney, the cardiovascular system is an important target for aldosterone. In the endothelium, it promotes the expression of epithelial sodium channels (ENaC) and modifies the morphology of cells in terms of mechanical stiffness, surface area and volume. Additionally, it renders the cells highly sensitive to small changes in extracellular sodium and potassium. In this context, the time course of aldosterone action is pivotal. In the fast (seconds to minutes), non-genomic signalling pathway vascular endothelial cells respond to aldosterone with transient swelling, softening and insertion of ENaC in the apical plasma membrane. In parallel, nitric oxide (NO) is released from the cells. In the long-term (hours), aldosterone has opposite effects: The mechanical stiffness increases, the cells shrink and NO production decreases. This leads to the conclusion that both the physiology and pathophysiology of aldosterone action in the vascular endothelium are closely related. Aldosterone, at concentrations in the physiological range and over limited time periods can stabilize blood pressure and regulate tissue perfusion while chronically high concentrations of this hormone over extended time periods impair sodium homeostasis promoting endothelial dysfunction and the development of tissue fibrosis.     

Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: Ménage à trois or ménage à quatre?

The mitogen-activated protein kinase (MAPK) signalling pathways play pivotal roles in cellular processes such as proliferation, apoptosis, gene regulation, differentiation, and cell motility. The typical mammalian MAPK pathways ERK1/2, JNK, p38^MAPK, and ERK5 operate through a concatenation of three successive phosphorylation events mediated by a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPKs phosphorylate substrates with distinct functions, including other protein kinases referred to as MAPK-activated protein kinases. One family of related MAPK-activated protein kinases includes MK2, MK3, and MK5. While it is generally accepted that MK2 and MK3 are bona fide substrates for p38^MAPK, the genuineness of MK5 as a p38^MAPK substrate is disputed. This review summarizes the findings pro and contra an authentic p38^MAPK-MK5 relationship, discusses possible explanations for these discrepancies, and proposes experiments that may help to unequivocally clarify whether MK5 is indeed a substrate for p38^MAPK.     

Plant–insect–pathogen interactions: a naturally complex ménage à trois

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Commensals, bacterial pathogens and intestinal inflammation: an intriguing ménage à trois

According to a classical view of bacterial-host interactions at intestinal surfaces, the commensal microbiota establishes tolerance, and invasive pathogens cause stereotypic inflammation. The reality is more complex, marked by a "ménage à trois" situation encompassing three emerging concepts: (1) pathogens take advantage of inflammation to cross the epithelial barrier, (2) pathogens reduce the commensal flora to invade their niche, and (3) pathogens express dedicated effectors that modulate inflammation.     

Regulation of myogenic stem cell behaviour by vessel cells: The "ménage à trois" of satellite cells,periendothelial cells and endothelial cells

In skeletal muscle, satellite cells, that are responsible of muscle repair, are localized close to capillaries. Although angiogenesis is known for a long time to be crucial for muscle repair and satellite cell survival, cellular interplays between vessel cells and satellite/myogenic cells have been poorly explored. We analyzed the interrelationships between myogenic cells, endothelial cells, and periendothelial cells that includes smooth muscle cells and endomysial fibroblasts. We found that endothelial cells strongly stimulate myogenic cell growth and, inversely, myogenic cells increase angiogenesis. VEGF plays a essential role in this bidirectional interaction. On the contrary, periendothelial cells promote the return to quiescence of a subset of muscle precursor cells to quiescence that ensures self-renewal of adult muscle stem cells. We have shown that Angiopoietin-1/Tie-2 signalling controls the entry into quiescence. We propose that during muscle regeneration, i.e. while vessels are not stabilized, endothelial cells and myogenic cells interact with each other to promote both myogenesis and angiogenesis, that have been shown to be concomitant processes in several models. On the other hand, once homeostasis of muscle is reached, the proximity of satellite cells and periendothelial cells allows the responsiveness of satellite cells, that bear Tie-2 receptor, to the secretion of Angiopoietin-1 by periendothelial cells, that, in the same time, stabilize vessels by promoting quiescence of endothelial cells.     

A ménage à trois made in heaven: G-protein-coupled receptors, lipids and TRP channels

Recent technical and conceptual advances in lipid analysis have given us a glimpse into the true versatility of the lipidome and the complexity of lipid signaling species. Progress alike in protein chemistry and genetics has presented us with new signal pathways and molecular mechanisms for the lipid actions. G-protein-coupled receptors (GPCR) appear to play a central role in the regulation of many lipid signals and are also themselves targets for some of these. TRP channels have recently been acknowledged as one of the most important GPCR effectors; in many cases the signals from GPCRs to TRPs are mediated via lipid signals. This review aims at presenting a view into the complex lipid signaling networks, their possible regulation by GPCRs and the signals transmitted to the TRP channels. Critical views and possible shortcomings in the composition of the studies are also presented.     

Plant meristems: a ménage à trois to end it all

Regulated termination of stem cell maintenance is required to complete reproductive development in plants. Two recent studies have revealed a new relationship for some old suspects; the WUSCHEL gene, which promotes indeterminancy, is involved as well as the floral regulators LEAFY and AGAMOUS.     

Risk predisposition for Crohn disease: a "ménage à trois" combining IRGM allele, miRNA and xenophagy

Susceptibility to Crohn disease (CD), an inflammatory bowel disease, is influenced by common variants at many loci like the exonic synonymous IRGM SNP (rs10065172, NM_001145805.1, c.313C>T). We recently showed that miR-196 is overexpressed in the inflammatory intestinal epithelia of individuals with CD and downregulates the IRGM protective (c.313C) but not the risk-associated (c.313T) allele. Eventually, loss of: IRGM/miRNA regulation compromises xenophagy. These results highlight a critical "ménage à trois" in risk susceptibility combining IRGM allele, miRNA and xenophagy.     

Risk predisposition for Crohn disease: A “ménage à trois” combining IRGM allele,miRNA and xenophagy

Susceptibility to Crohn disease (CD), an inflammatory bowel disease, is influenced by common variants at many loci like the exonic synonymous IRGM SNP (rs10065172, NM_001145805.1, c.313C>T). We recently showed that miR-196 is overexpressed in the inflammatory intestinal epithelia of individuals with CD and downregulates the IRGM protective (c.313C) but not the risk-associated (c.313T) allele. Eventually, loss of

IRGM/miRNA regulation compromises xenophagy. These results highlight a critical “ménage à trois” in risk susceptibility combining IRGM allele, miRNA and xenophagy.     

Ménage à trois on Macquarie Island: hybridization among three species of fur seal (Arctocephalus spp.) following historical population extinction

Human-induced changes to natural systems can cause major disturbances to fundamental ecological and population processes and result in local extinctions and secondary contacts between formerly isolated species. Extensive fur seal harvesting during the nineteenth century on Macquarie Island (subantarctic) resulted in extinction of the original population. Recolonization by three species has been slow and complex, characterized by the establishment of breeding groups of Antarctic and subantarctic fur seals (Arctocephalus gazella and Arctocephalus tropicalis) and presumed nonbreeding (itinerant) male New Zealand fur seals (Arctocephalus forsteri). One thousand and seven pups from eight annual cohorts (1992-2003) were analysed using mitochondrial control region data (RFLP) and 10 microsatellite loci to estimate species composition and hybridization. Antarctic fur seals predominated, but hybridization occurred between all three species (17-30% of all pups). Involvement of New Zealand fur seals was unexpected as females are absent and males are not observed to hold territories during the breeding season. The proportion of hybrids in the population has fallen over time, apparently owing to substantial influxes of pure Antarctic and subantarctic individuals and non-random mating. Over 50% of New Zealand hybrids and 43% of Antarctic-subantarctic hybrids were not F(1), which indicates some degree of hybrid reproductive success, and this may be underestimated: simulations showed that hybrids become virtually undetectable by the third generation of backcrossing. While human impacts seem to have driven novel hybridization in this population, the present 'time slices' analysis suggests some biological resistance to complete homogenization.