Alteration of the late endocytic pathway in Charcot–Marie–Tooth type 2B disease

The small GTPase RAB7A regulates late stages of the endocytic pathway and plays specific roles in neurons, controlling neurotrophins trafficking and signaling, neurite outgrowth and neuronal migration. Mutations in the RAB7A gene cause the autosomal dominant Charcot–Marie–Tooth type 2B (CMT2B) disease, an axonal peripheral neuropathy. As several neurodegenerative diseases are caused by alterations of endocytosis, we investigated whether CMT2B-causing mutations correlate with changes in this process. To this purpose, we studied the endocytic pathway in skin fibroblasts from healthy and CMT2B individuals. We found higher expression of late endocytic proteins in CMT2B cells compared to control cells, as well as higher activity of cathepsins and higher receptor degradation activity. Consistently, we observed an increased number of lysosomes, accompanied by higher lysosomal degradative activity in CMT2B cells. Furthermore, we found increased migration and increased RAC1 and MMP-2 activation in CMT2B compared to control cells. To validate these data, we obtained sensory neurons from patient and control iPS cells, to confirm increased lysosomal protein expression and lysosomal activity in CMT2B-derived neurons. Altogether, these results demonstrate that in CMT2B patient-derived cells, the endocytic degradative pathway is altered, suggesting that higher lysosomal activity contributes to neurodegeneration occurring in CMT2B

Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs

Mammalian homologs of the yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains to be defined. Recently, syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was shown to bind mAtg8s. Here we broadened the analysis of potential mAtg8-SNARE interactions and identified LC3-interacting regions (LIRs) in several SNAREs. Syntaxin 16 (Stx16), and its cognate SNARE partners all have LIR motifs and bind mAtg8s. A knockout in STX16 caused defects in lysosome biogenesis whereas a double STX16 and STX17 knockout completely blocked autophagic flux and decreased mitophagy, pexophagy, xenophagy, and ribophagy. Mechanistic analyses revealed that mAtg8s and Stx16 maintained several aspects of lysosomal compartments including their functionality as platforms for active mTOR. These findings reveal a broad direct interaction of mAtg8s with SNAREs with impact on membrane remodeling in eukaryotic cells and expand the roles of mAtg8s to lysosome biogenesis.</p

Tea drinking and cognitive function in oldest-old Chinese

10.1007/s12603-012-0077-1The Journal of Nutrition, Health & Aging169754-75

Soil net nitrogen mineralisation across global grasslands

Soil nitrogen mineralisation (N-min), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net N-min) varies with soil properties and climate. However, because most global-scale assessments of net N-min are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net N-min across 30 grasslands worldwide. We find that realised N-min is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential N-min only weakly correlates with realised N-min, but contributes to explain realised net N-min when combined with soil and climatic variables. We provide novel insights of global realised soil net N-min and show that potential soil net N-min data available in the literature could be parameterised with soil and climate data to better predict realised N-min

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform

The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes

Nitrogen but not phosphorus addition affects symbiotic N-2 fixation by legumes in natural and semi-natural grasslands located on four continents

Background and aims: The amount of nitrogen (N) derived from symbiotic N-2 fixation by legumes in grasslands might be affected by anthropogenic N and phosphorus (P) inputs, but the underlying mechanisms are not known.Methods: We evaluated symbiotic N-2 fixation in 17 natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the N-15 natural abundance method.Results: N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N-2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials.Conclusion: Our results reveal that N addition mainly impacts symbiotic N-2 fixation via reduced biomass of legumes rather than changes in N-2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N-2 fixation in grasslands, and these effects cannot be reversed by additional P amendment

Herbivory and nutrients shape grassland soil seed banks

Anthropogenic nutrient enrichment and shifts in herbivory can lead to dramatic changes in the composition and diversity of aboveground plant communities. In turn, this can alter seed banks in the soil, which are cryptic reservoirs of plant diversity. Here, we use data from seven Nutrient Network grassland sites on four continents, encompassing a range of climatic and environmental conditions, to test the joint effects of fertilization and aboveground mammalian herbivory on seed banks and on the similarity between aboveground plant communities and seed banks. We find that fertilization decreases plant species richness and diversity in seed banks, and homogenizes composition between aboveground and seed bank communities. Fertilization increases seed bank abundance especially in the presence of herbivores, while this effect is smaller in the absence of herbivores. Our findings highlight that nutrient enrichment can weaken a diversity maintaining mechanism in grasslands, and that herbivory needs to be considered when assessing nutrient enrichment effects on seed bank abundance.EEA Santa CruzFil: Eskelinen, Anu. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eskelinen, Anu. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Eskelinen, Anu. University of Oulu. Ecology & Genetics; FinlandiaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Jessen, Maria Theresa. German Centre for Integrative Biodiversity Research; AlemaniaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Bahamonde, Hector Alejandro. Universidad Nacional de La Plata. Ciencias Agrarias y Forestales; Argentina.Fil: Bakker, Jonathan D. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Caldeira, Maria C. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Harpole, William Stanley. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Harpole, William Stanley. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Harpole, William Stanley. Martin Luther University. Institute of Biology; AlemaniaFil: Jia, Meiyu. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Jia, Meiyu. East China University of Technology. School of Water Resources & Environmental Engineering; China.Fil: Jia, Meiyu. Beijing Normal University. College of Life Sciences; China.Fil: Lannes, Luciola S. São Paulo State University-UNESP. Department of Biology and Animal Sciences; Brasil.Fil: Nogueira, Carla. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Venterink, Harry Olde. Vrije Universiteit Brussel (VUB). Department of Biology; BélgicaFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Porath-Krause, Anita J. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Seabloom, Eric William. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Georgia. Odum School of Ecology; Estados UnidosFil: Tognetti, Pedro M. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Tognetti, Pedro M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA); Argentina.Fil: Tognetti, Pedro M. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Yasui, Simone-Louise E. Queensland University of Technology. School of Biological and Environmental Sciences; Australia.Fil: Virtanen, Risto. University of Oulu. Ecology & Genetics; FinlandiaFil: Sullivan, Lauren L. University of Missouri. Division of Biological Sciences; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Department of Plant Biology; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. W. K. Kellogg Biological Station; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Ecology, Evolution and Behavior Program; Estados Unido

The mechanism of macroautophagy: The movie

This animated movie presents the mechanism of macroautophagy, hereafter autophagy, by showing the molecular features of the formation of autophagosomes, the hallmark organelle of this intracellular catabolic pathway. It is based on our current knowledge and it also illustrates how autophagosomes can recognize and eliminate selected cargoes.</p