@article{MorgensternPeikertLuebbertetal.2021, author = {Morgenstern, Marcel and Peikert, Christian D. and L{\"u}bbert, Philipp and Suppanz, Ida and Klemm, Cinzia and Alka, Oliver and Steiert, Conny and Naumenko, Nataliia and Schendzielorz, Alexander and Melchionda, Laura and M{\"u}hlh{\"a}user, Wignand W. D. and Knapp, Bettina and Busch, Jakob D. and Stiller, Sebastian B. and Dannenmaier, Stefan and Lindau, Caroline and Licheva, Mariya and Eickhorst, Christopher and Galbusera, Riccardo and Zerbes, Ralf M. and Ryan, Michael T. and Kraft, Claudine and Kozjak-Pavlovic, Vera and Drepper, Friedel and Dennerlein, Sven and Oeljeklaus, Silke and Pfanner, Nikolaus and Wiedemann, Nils and Warscheid, Bettina}, title = {Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context}, series = {Cell Metabolism}, volume = {33}, journal = {Cell Metabolism}, doi = {10.1016/j.cmet.2021.11.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371114}, pages = {2464-2483}, year = {2021}, abstract = {Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases. Different views exist on the composition of the human mitochondrial proteome. We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). We identified interactors of translocases, respiratory chain, and ATP synthase assembly factors. The abundance of MitoCoP proteins covers six orders of magnitude and amounts to 7\% of the cellular proteome with the chaperones HSP60-HSP10 being the most abundant mitochondrial proteins. MitoCoP dynamics spans three orders of magnitudes, with half-lives from hours to months, and suggests a rapid regulation of biosynthesis and assembly processes. 460 MitoCoP genes are linked to human diseases with a strong prevalence for the central nervous system and metabolism. MitoCoP will provide a high-confidence resource for placing dynamics, functions, and dysfunctions of mitochondria into the cellular context.}, language = {en} } @article{MannucciDangHuberetal.2021, author = {Mannucci, Ilaria and Dang, Nghi D. P. and Huber, Hannes and Murry, Jaclyn B. and Abramson, Jeff and Althoff, Thorsten and Banka, Siddharth and Baynam, Gareth and Bearden, David and Beleza-Meireles, Ana and Benke, Paul J. and Berland, Siren and Bierhals, Tatjana and Bilan, Frederic and Bindoff, Laurence A. and Braathen, Geir Julius and Busk, {\O}yvind L. and Chenbhanich, Jirat and Denecke, Jonas and Escobar, Luis F. and Estes, Caroline and Fleischer, Julie and Groepper, Daniel and Haaxma, Charlotte A. and Hempel, Maja and Holler-Managan, Yolanda and Houge, Gunnar and Jackson, Adam and Kellogg, Laura and Keren, Boris and Kiraly-Borri, Catherine and Kraus, Cornelia and Kubisch, Christian and Le Guyader, Gwenael and Ljungblad, Ulf W. and Brenman, Leslie Manace and Martinez-Agosto, Julian A. and Might, Matthew and Miller, David T. and Minks, Kelly Q. and Moghaddam, Billur and Nava, Caroline and Nelson, Stanley F. and Parant, John M. and Prescott, Trine and Rajabi, Farrah and Randrianaivo, Hanitra and Reiter, Simone F. and Schuurs-Hoeijmakers, Janneke and Shieh, Perry B. and Slavotinek, Anne and Smithson, Sarah and Stegmann, Alexander P. A. and Tomczak, Kinga and Tveten, Kristian and Wang, Jun and Whitlock, Jordan H. and Zweier, Christiane and McWalter, Kirsty and Juusola, Jane and Quintero-Rivera, Fabiola and Fischer, Utz and Yeo, Nan Cher and Kreienkamp, Hans-J{\"u}rgen and Lessel, Davor}, title = {Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders}, series = {Genome Medicine}, volume = {13}, journal = {Genome Medicine}, doi = {10.1186/s13073-021-00900-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306477}, year = {2021}, abstract = {Background We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder. Methods Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays. Results We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype. Conclusions Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.}, language = {en} } @article{MaasBrandlHussainetal.2021, author = {Maas, Bea and Brandl, Manuela and Hussain, Raja Imran and Frank, Thomas and Zulka, Klaus Peter and Rabl, Dominik and Walcher, Ronnie and Moser, Dietmar}, title = {Functional traits driving pollinator and predator responses to newly established grassland strips in agricultural landscapes}, series = {Journal of Applied Ecology}, volume = {58}, journal = {Journal of Applied Ecology}, doi = {10.1111/1365-2664.13892}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369992}, pages = {1728-1737}, year = {2021}, abstract = {Agricultural biodiversity and associated ecosystem functions are declining at alarming rates due to widespread land use intensification. They can only be maintained through targeted landscape management that supports species with different habitat preferences, dispersal capacities and other functional traits that determine their survival. However, we need better understanding whether short-term measures can already improve functional diversity in European agroecosystems. We investigated spatio-temporal responses of bees (solitary bees, bumblebees and honey bees), hoverflies, carabid beetles and spiders to newly established grassland strips in Lower Austria over 3 years, and along a distance gradient to old grasslands. Specifically, we asked if new grasslands, compared to old grasslands and cereal fields, serve as temporal dispersal habitat or corridor, and how species-specific traits affect dispersal patterns. Using a trait-based functional diversity approach, we investigated year and distance effects for nine selected key traits per taxon (e.g. body size, feeding guild and habitat preferences). Our results show that the functional diversity of predators and pollinators (i.e. functional richness and evenness), as well as community-weighted means of selected key traits in new grasslands significantly differed from adjacent cereal fields, but only slowly adjusted to adjacent old grasslands. These effects significantly decreased with increasing distance to old grasslands for carabids and spiders, but not for mobile bees and hoverflies. Synthesis and applications. Over 3 years, newly established grassland strips supported larger sized and actively foraging/hunting species in the agricultural landscape. Adjacent crops likely benefit from such measures through enhanced functional diversity and related ecosystem services. However, our results also suggest that 3-year period is too short to enhance the occurrence of pollinators and epigeic predators in new grasslands. Agri-environment measures need to be complemented by the conservation of permanent habitats to effectively maintain species and functional diversity. Our findings should be acknowledged by European policy and agricultural decision makers for the design of more effective agri-environment schemes, taking into account trait-dependent species responses to land use change.}, language = {en} } @article{LuBierbachOrmannsetal.2021, author = {Lu, Yuan and Bierbach, David and Ormanns, Jenny and Warren, Wesley C. and Walter, Ronald B. and Schartl, Manfred}, title = {Fixation of allelic gene expression landscapes and expression bias pattern shape the transcriptome of the clonal Amazon molly}, series = {Genome Research}, volume = {31}, journal = {Genome Research}, doi = {10.1101/gr.268870.120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369578}, pages = {372-379}, year = {2021}, abstract = {The Amazon molly is a unique clonal fish species that originated from an interspecies hybrid between Poecilia species P. mexicana and P. latipinna. It reproduces by gynogenesis, which eliminates paternal genomic contribution to offspring. An earlier study showed that Amazon molly shows biallelic expression for a large portion of the genome, leading to two main questions: (1) Are the allelic expression patterns from the initial hybridization event stabilized or changed during establishment of the asexual species and its further evolution? (2) Is allelic expression biased toward one parental allele a stochastic or adaptive process? To answer these questions, the allelic expression of P. formosa siblings was assessed to investigate intra- and inter-cohort allelic expression variability. For comparison, interspecies hybrids between P. mexicana and P. latipinna were produced in the laboratory to represent the P. formosa ancestor. We have identified inter-cohort and intra-cohort variation in parental allelic expression. The existence of inter-cohort divergence suggests functional P. formosa allelic expression patterns do not simply reflect the atavistic situation of the first interspecies hybrid but potentially result from long-term selection of transcriptional fitness. In addition, clonal fish show a transcriptional trend representing minimal intra-clonal variability in allelic expression patterns compared to the corresponding hybrids. The intra-clonal similarity in gene expression translates to sophisticated genetic functional regulation at the individuum level. These findings suggest the parental alleles inherited by P. formosa form tightly regulated genetic networks that lead to a stable transcriptomic landscape within clonal individuals.}, language = {en} } @article{LozaValdesMayerKassoufetal.2021, author = {Loza-Valdes, Angel and Mayer, Alexander E and Kassouf, Toufic and Trujillo-Viera, Jonathan and Schmitz, Werner and Dziaczkowski, Filip and Leitges, Michael and Schlosser, Andreas and Sumara, Grzegorz}, title = {A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism}, series = {Life Science Alliance}, volume = {4}, journal = {Life Science Alliance}, doi = {10.26508/lsa.202000863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369560}, year = {2021}, abstract = {Members of the protein kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified more than 300 putative targets of PKD3. Furthermore, biochemical analysis revealed that PKD3 regulates cAMP-dependent PKA activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes. Therefore, our data indicate that PKD3 might play a role in the hepatic response to glucagon.}, language = {en} } @article{LiKuhnZukowskaKasprzyketal.2021, author = {Li, Yuanyue and Kuhn, Michael and Zukowska-Kasprzyk, Joanna and Hennrich, Marco L. and Kastritis, Panagiotis L. and O'Reilly, Francis J. and Phapale, Prasad and Beck, Martin and Gavin, Anne-Claude and Bork, Peer}, title = {Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum}, series = {PLOS ONE}, volume = {16}, journal = {PLOS ONE}, doi = {10.1371/journal.pone.0254429}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364299}, year = {2021}, abstract = {Protein-metabolite interactions play an important role in the cell's metabolism and many methods have been developed to screen them in vitro. However, few methods can be applied at a large scale and not alter biological state. Here we describe a proteometabolomic approach, using chromatography to generate cell fractions which are then analyzed with mass spectrometry for both protein and metabolite identification. Integrating the proteomic and metabolomic analyses makes it possible to identify protein-bound metabolites. Applying the concept to the thermophilic fungus Chaetomium thermophilum, we predict 461 likely protein-metabolite interactions, most of them novel. As a proof of principle, we experimentally validate a predicted interaction between the ribosome and isopentenyl adenine.}, language = {en} } @article{LiZhangFanetal.2021, author = {Li, Ming and Zhang, Rui and Fan, Guangyi and Xu, Wenteng and Zhou, Qian and Wang, Lei and Li, Wensheng and Pang, Zunfang and Yu, Mengjun and Liu, Qun and Liu, Xin and Schartl, Manfred and Chen, Songlin}, title = {Reconstruction of the Origin of a Neo-Y Sex Chromosome and Its Evolution in the Spotted Knifejaw, Oplegnathus punctatus}, series = {Molecular Biology and Evolution}, volume = {38}, journal = {Molecular Biology and Evolution}, doi = {10.1093/molbev/msab056}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364215}, pages = {2615-2626}, year = {2021}, abstract = {Sex chromosomes are a peculiar constituent of the genome because the evolutionary forces that fix the primary sex-determining gene cause genic degeneration and accumulation of junk DNA in the heterogametic partner. One of the most spectacular phenomena in sex chromosome evolution is the occurrence of neo-Y chromosomes, which lead to X1X2Y sex-determining systems. Such neo-sex chromosomes are critical for understanding the processes of sex chromosome evolution because they rejuvenate their total gene content. We assembled the male and female genomes at the chromosome level of the spotted knifejaw (Oplegnathus punctatus), which has a cytogenetically recognized neo-Y chromosome. The full assembly and annotation of all three sex chromosomes allowed us to reconstruct their evolutionary history. Contrary to other neo-Y chromosomes, the fusion to X2 is quite ancient, estimated at 48 Ma. Despite its old age and being even older in the X1 homologous region which carries a huge inversion that occurred as early as 55-48 Ma, genetic degeneration of the neo-Y appears to be only moderate. Transcriptomic analysis showed that sex chromosomes harbor 87 genes, which may serve important functions in the testis. The accumulation of such male-beneficial genes, a large inversion on the X1 homologous region and fusion to X2 appear to be the main drivers of neo-Y evolution in the spotted knifejaw. The availability of high-quality assemblies of the neo-Y and both X chromosomes make this fish an ideal model for a better understanding of the variability of sex determination mechanisms and of sex chromosome evolution.}, language = {en} } @article{LetunicBork2021, author = {Letunic, Ivica and Bork, Peer}, title = {Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, doi = {10.1093/nar/gkab301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363803}, pages = {W293-W296}, year = {2021}, abstract = {The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. iTOL version 5 introduces a completely new tree display engine, together with numerous new features. For example, a new dataset type has been added (MEME motifs), while annotation options have been expanded for several existing ones. Node metadata display options have been extended and now also support non-numerical categorical values, as well as multiple values per node. Direct manual annotation is now available, providing a set of basic drawing and labeling tools, allowing users to draw shapes, labels and other features by hand directly onto the trees. Support for tree and dataset scales has been extended, providing fine control over line and label styles. Unrooted tree displays can now use the equal-daylight algorithm, proving a much greater display clarity. The user account system has been streamlined and expanded with new navigation options and currently handles >1 million trees from >70 000 individual users.}, language = {en} } @article{LehmannJorgensenFratzetal.2021, author = {Lehmann, Julian and J{\o}rgensen, Morten E. and Fratz, Stefanie and M{\"u}ller, Heike M. and Kusch, Jana and Scherzer, S{\"o}nke and Navarro-Retamal, Carlos and Mayer, Dominik and B{\"o}hm, Jennifer and Konrad, Kai R. and Terpitz, Ulrich and Dreyer, Ingo and Mueller, Thomas D. and Sauer, Markus and Hedrich, Rainer and Geiger, Dietmar and Maierhofer, Tobias}, title = {Acidosis-induced activation of anion channel SLAH3 in the flooding-related stress response of Arabidopsis}, series = {Current Biology}, volume = {31}, journal = {Current Biology}, doi = {10.1016/j.cub.2021.06.018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363320}, pages = {3575-3585}, year = {2021}, abstract = {Plants, as sessile organisms, gained the ability to sense and respond to biotic and abiotic stressors to survive severe changes in their environments. The change in our climate comes with extreme dry periods but also episodes of flooding. The latter stress condition causes anaerobiosis-triggered cytosolic acidosis and impairs plant function. The molecular mechanism that enables plant cells to sense acidity and convey this signal via membrane depolarization was previously unknown. Here, we show that acidosis-induced anion efflux from Arabidopsis (Arabidopsis thaliana) roots is dependent on the S-type anion channel AtSLAH3. Heterologous expression of SLAH3 in Xenopus oocytes revealed that the anion channel is directly activated by a small, physiological drop in cytosolic pH. Acidosis-triggered activation of SLAH3 is mediated by protonation of histidine 330 and 454. Super-resolution microscopy analysis showed that the increase in cellular proton concentration switches SLAH3 from an electrically silent channel dimer into its active monomeric form. Our results show that, upon acidification, protons directly switch SLAH3 to its open configuration, bypassing kinase-dependent activation. Moreover, under flooding conditions, the stress response of Arabidopsis wild-type (WT) plants was significantly higher compared to SLAH3 loss-of-function mutants. Our genetic evidence of SLAH3 pH sensor function may guide the development of crop varieties with improved stress tolerance.}, language = {en} } @article{LeProvostThieleWestphaletal.2021, author = {Le Provost, Ga{\"e}tane and Thiele, Jan and Westphal, Catrin and Penone, Caterina and Allan, Eric and Neyret, Margot and van der Plas, Fons and Ayasse, Manfred and Bardgett, Richard D. and Birkhofer, Klaus and Boch, Steffen and Bonkowski, Michael and Buscot, Francois and Feldhaar, Heike and Gaulton, Rachel and Goldmann, Kezia and Gossner, Martin M. and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Renner, Swen and Scherreiks, Pascal and Sikorski, Johannes and Baulechner, Dennis and Bl{\"u}thgen, Nico and Bolliger, Ralph and B{\"o}rschig, Carmen and Busch, Verena and Chist{\´e}, Melanie and Fiore-Donno, Anna Maria and Fischer, Markus and Arndt, Hartmut and Hoelzel, Norbert and John, Katharina and Jung, Kirsten and Lange, Markus and Marzini, Carlo and Overmann, J{\"o}rg and Paŝalić, Esther and Perović, David J. and Prati, Daniel and Sch{\"a}fer, Deborah and Sch{\"o}ning, Ingo and Schrumpf, Marion and Sonnemann, Ilja and Steffan-Dewenter, Ingolf and Tschapka, Marco and T{\"u}rke, Manfred and Vogt, Juliane and Wehner, Katja and Weiner, Christiane and Weisser, Wolfgang and Wells, Konstans and Werner, Michael and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Zaitsev, Andrey S. and Manning, Peter}, title = {Contrasting responses of above- and belowground diversity to multiple components of land-use intensity}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23931-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371552}, year = {2021}, abstract = {Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.}, language = {en} }