Cell Biology of Galectins

Galectins are a family of soluble beta-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. There are sixteen recognized mammalian galectin genes, and their expression profiles are very different between cell types, tissues, and species. This Special Issue covers recent progress in the field of the cell biology of galectins, relevant concepts of galectin regulatory mechanisms, and biomedical aspects of these unique multifunctional proteins

Microbial Virulence Factors

Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease. This broad definition comprises secreted products such as toxins, enzymes, exopolysaccharides, as well as cell surface structures such as capsules, lipopolysaccharides, glyco- and lipoproteins. Intracellular changes in metabolic regulatory networks, governed by protein sensors/regulators and non-coding regulatory RNAs, are also known to contribute to virulence. Furthermore, some secreted microbial products have the ability to enter the host cell and manipulate their machinery, contributing to the success of the infection. The knowledge, at the molecular level, of the biology of microbial pathogens and their virulence factors is central in the development of novel therapeutic molecules and strategies to combat microbial infections. The present collection comprises state of the art research and review papers on virulence factors and mechanisms of a wide range of bacterial and fungal pathogens for humans, animals, and plants, thus reflecting the impact of microorganisms in health and economic human activities, and the importance of the topic

A mutagenic approach to elucidating aquaporin function

Aquaporins (AQPs) are transmembrane proteins that facilitate the movement of water molecules across biological membrane by osmosis. Green fluorescent protein-tagged aquaporin 4 relocalized to the plasma membrane of HEK293 cells in response to reduced tonicity and this phenomenon was reproduced for endogenous AQP4 in primary astrocyte cultures. The mechanism was dependent on phosphorylation at serine-276 by PKA and required activation of CaM. AQP4 knockout animals are protected from brain edema so pharmacologically modulating the subcellular localization of AQP4 may provide a platform for an alternative or complementary approach to hyperosmotic solution based edema therapies. Using the same methodology, we also describe some of the factors controlling AQP5 plasma membrane abundance. AQPs have a signature aromatic/arginine (ar/R) motif that is thought to aid in solute selectivity. Mutants of AQP4 in this region permitted the passage of small solutes differently to AQP1, questioning the validity of a generalized model of AQP solute exclusion. Furthermore, the relative selectivity for glycerol and urea of AQPs could be modulated independently of the physical size of the Ar/R region, suggesting that lack of solute exclusion and solute selectivity are not the same thing. AQPs retain homotetrameric quaternary structures, but the structural basis and functional relevance of this assembly is not known. Mutants of an intracellular loop of AQP4 had reduced ability to form tetramers and, despite no change in constitutive levels of membrane localization or water permeability, had reduced capacity to relocalize in response to hypotonicity

Abstracts of 51st EASD Annual Meeting

Background and aims: Presence and frequency of beta cell (BC) dysfunction(BCD) and insulin resistance (IR) in patients with newly diagnosedtype 2 diabetes mellitus (NDT2D) are imperfectly known, becauseprevious studies used small cohorts and/or only surrogate indexes of BCfunction and IR.We sought to assess BC function and IR with state-of-artmethods in the VNDS.Materials and methods: In 712 GADA-negative, drug naïve, consecutiveItalian NDT2D patients we assessed: 1. standard parameters; 2. insulinsensitivity (IS) by the euglycaemic insulin clamp); 3. BC functionby state-of-art modeling of prolonged (5 hours) OGTT-derived glucose/C-peptide curves. Thresholds for BCD and IR were the 25th percentilesof BC function and IS assessed with the same methods of the VNDS inItalian subjects with normal glucose regulation of the GENFIEV (n=340)and GISIR (n=386) studies, respectively.Results: In the VNDS, 89.8% [95% C.I.: 87.6 - 92.0%] and87.8% [85.4 - 90.2] patients had BCD and IR, respectively. Patientswith only one defect were 19.7% [16.8 - 22.6]. IsolatedBCD and isolated IR were present in 10.9% [8.6 - 13.2] and8.9% [6.8 - 11.0] patients, respectively. Coexistence of BCDand IR was observed in 78.9% [75.9 - 81.9] of the patients.1.4% [0.5 - 2.3] of the patients had no detectable alterations inBC function and IS. Patients (19.7%) with only one metabolicdefect had lower BMI, fasting glucose, HbA1c, triglycerides andBC function, and higher HDL-cholesterol and IS than patientswith both BCD and IR (p<0.01 or less after Bonferroni’scorrection).Conclusion: In conclusion, in NDT2DM patients: 1. at least 75.9% haveboth BCD and IR; 2. At least 87.6% and 85.4% have BCD and IR,respectively; 3. At least 16.8% have only one defect and a significantlydifferent (milder) metabolic phenotype compared to patients with bothdefects. These findings may be relevant to therapeutic strategies centeredon the metabolic phenotype of the patient.Clinical Trial Registration Number: NCT00879801; NCT01526720Supported by: University of Veron