High Sugar-Induced Insulin Resistance in Drosophila Relies on the Lipocalin Neural Lazarillo

In multicellular organisms, insulin/IGF signaling (IIS) plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD) that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D) patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz), a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome

Role of SNX16 in the Dynamics of Tubulo-Cisternal Membrane Domains of Late Endosomes

In this paper, we report that the PX domain-containing protein SNX16, a member of the sorting nexin family, is associated with late endosome membranes. We find that SNX16 is selectively enriched on tubulo-cisternal elements of this membrane system, whose highly dynamic properties and formation depend on intact microtubules. By contrast, SNX16 was not found on vacuolar elements that typically contain LBPA, and thus presumably correspond to multivesicular endosomes. We conclude that SNX16, together with its partner phosphoinositide, define a highly dynamic subset of late endosomal membranes, supporting the notion that late endosomes are organized in distinct morphological and functional regions. Our data also indicate that SNX16 is involved in tubule formation and cholesterol transport as well as trafficking of the tetraspanin CD81, suggesting that the protein plays a role in the regulation of late endosome membrane dynamics

SNX12 Role in Endosome Membrane Transport

In this paper, we investigated the role of sorting nexin 12 (SNX12) in the endocytic pathway. SNX12 is a member of the PX domain-containing sorting nexin family and shares high homology with SNX3, which plays a central role in the formation of intralumenal vesicles within multivesicular endosomes. We found that SNX12 is expressed at very low levels compared to SNX3. SNX12 is primarily associated with early endosomes and this endosomal localization depends on the binding to 3-phosphoinositides. We find that overexpression of SNX12 prevents the detachment (or maturation) of multivesicular endosomes from early endosomes. This in turn inhibits the degradative pathway from early to late endosomes/lysosomes, much like SNX3 overexpression, without affecting endocytosis, recycling and retrograde transport. In addition, while previous studies showed that Hrs knockdown prevents EGF receptor sorting into multivesicular endosomes, we find that overexpression of SNX12 restores the sorting process in an Hrs knockdown background. Altogether, our data show that despite lower expression level, SNX12 shares redundant functions with SNX3 in the biogenesis of multivesicular endosomes

Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System

During embryonic development of the motor system of Drosophila, motorneurons target their dendrites to different regions along the body axis in response to midline guidance cues

Addressing crop interactions within cropping systems in LCA

Purpose The focus of the Life Cycle Assessment (LCA) of an agricultural plant product is typically on one crop. However, isolating one crop from the cropping system that it belongs to is often challenging because the crops are often interlinked with the other crops in the cropping system. The main objectives of this discussion article are: i) to discuss the characteristics of cropping systems which might affect the LCA methodology, ii) to discuss the advantages and the disadvantages of the current available methods for the life cycle assessment of cropping systems and iii) to offer a framework to carry out LCA of crops and cropping systems. Methods The definition of cropping systems is provided together with a description of two types of LCA: product LCA and system LCA. The LCA issues related to cropping systems characteristics have been classified as 1) crop interrelationship, 2) crop management and emissions, and 3) functional unit issues. The LCA approaches presented are: Cropping System, Allocation approaches, Crop-by-Crop approach, Combined approaches. The various approaches are described together with their advantages and disadvantages, applicability, comprehensiveness and accuracy. Results and discussion The Cropping System approach is best suited for system LCA. For product LCA, none of the methods is fully exhaustive and accurate. The crop sequence approach takes into consideration cropping systems issues if they happen within the year or season and cannot be applied for intercropping and agroforestry systems. The allocation approaches take into consideration cropping system effects by establishing a mathematical relationship between crops present in the cropping systems. The Model for integrative Life Cycle Assessment in Agriculture (MiLA) approach considers cropping systems issues if they are related to multiproduct and nutrient cycling; while the Crop-by-Crop approach is highly affected by assumptions and considers cropping system issues only if they are related to the analysed crop. Conclusions Each LCA approach presents advantages and disadvantages. For system LCA, the Cropping Systems approach is recommended. For product LCA, environmental burdens should be attributed applying the following hierarchy: 1) attributed to the crop if based on a clear causality; 2) attributed with combined approaches and specific criteria; 3) attributed with allocation approaches and generic criteria. These approaches should be combined with the Cropping System approach