Connecting the dots: from nanodomains to physiological functions of REMORINs

REMORINs (REMs) are a plant-specific protein family, proposed regulators of membrane-associated molecular assemblies and well-established markers of plasma membrane nanodomains. REMs play a diverse set of functions in plant interactions with pathogens and symbionts, responses to abiotic stresses, hormone signaling and cell-to-cell communication. In this review, we highlight the established and more putative roles of REMs throughout the literature. We discuss the physiological functions of REMs, the mechanisms underlying their nanodomain-organization and their putative role as regulators of nanodomain-associated molecular assemblies. Furthermore, we discuss how REM phosphorylation may regulate their functional versatility. Overall, through data-mining and comparative analysis of the literature, we suggest how to further study the molecular mechanisms underpinning the functions of REMs.     

Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation

Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease.     

Complex patterns in phytoplankton and microeukaryote diversity along the estuarine continuum

Estuaries and coastal lagoons are included within the transitional waters category, according to the Water Framework Directive. However, criteria for their differentiation and characterisation are still under discussion and require more research. In particular, detailed observations of biodiversity in more complex transitional and coastal waters are lacking. Microscopic and molecular analyses were therefore used to investigate phytoplankton diversity and spatial community structure, in early spring, along the freshwater-to-marine continuum of the Segura River (Spain), an intensively regulated semiarid basin discharging into the Mediterranean Sea. In addition to the salinity gradient as the major factor determining taxa distribution, influence of multiple anthropogenic and climatic impacting factors (drought, confined waters, irrigation canal) leads to a significant spatial heterogeneity of the aquatic habitat types associated with variations in community composition. Several shifts within the phytoplankton distribution pattern along the continuum are revealed using multivariate analyses. An impressive bloom of the cryptophyte Plagioselmis prolonga occurred in the mixing zone, associated with a typical euryhaline community indicative of eutrophication. The 18S rDNA diversity revealed a microeukaryotic richness including several little-known groups, heterotrophic representatives, and potential parasites. By combining morphological and molecular approaches we revealed the presence of a ‘hidden’ diversity often neglected in traditional surveys.     

Characterization of the cell of origin for small cell lung cancer

Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer that affects more than 200,000 people worldwide every year with a very high mortality rate. Here, we used a mouse genetics approach to characterize the cell of origin for SCLC; in this mouse model, tumors are initiated by the deletion of the Rb and p53 tumor suppressor genes in the lung epithelium of adult mice. We found that mouse SCLCs often arise in the lung epithelium, where neuroendocrine cells are located, and that the majority of early lesions were composed of proliferating neuroendocrine cells. In addition, mice in which Rb and p53 are deleted in a variety of non-neuroendocrine lung epithelial cells did not develop SCLC. These data indicate that SCLC likely arises from neuroendocrine cells in the lung.Key words: Rb, p53, SCLC, cell of origin, cancer, lung, neuroendocrine     

Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(η6-p-MeC6H4Pr i )2Ru2(SC6H4-p-X)3]+: synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential

A series of cationic dinuclear p-cymene ruthenium trithiophenolato complexes of the type [(η(6)-p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p-X)(3)](+) (1 X is H, 2 X is Me, 3 X is Ph, 4 X is Br, 5 X is OH, 6 X is NO(2), 7 X is OMe, 8 X is CF(3), 9 X is F, 10 X is Pr(i), 11 X is Bu(t)) have been synthesized from the reaction of [(η(6)-p-MeC(6)H(4)Pr(i))RuCl(2)](2) with the corresponding thiol, isolated as the chloride salts, and further studied for their electrochemical properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidation. Complex 1 was also compared with the benzene and hexamethylbenzene analogues [(η(6)-C(6)H(6))(2)Ru(2)(SC(6)H(5))(3)](+) (12) and [(η(6)-C(6)Me(6))(2)Ru(2)(SC(6)H(5))(3)](+) (13). The most active compound [11]Cl was structurally studied by single-crystal X-ray diffraction analysis. The concentrations corresponding to 50 % inhibition of cancer cell growth (IC(50) values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC(50) value of 0.03 μM in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidation of GSH, although there is no clear correlation between the IC(50) values and the turnover frequencies at about 50 % conversion. However, the cytotoxicity is tentatively correlated to the physicochemical properties of the compounds determined by the electronic influence of the substituents X (Hammett constants σ(p)) and the lipophilicity of the thiols p-XC(6)H(4)SH (calculated log P parameters).     

Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation

The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences.