@article{15151,
abstract = {Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair.},
author = {Michael, Alicia and Thomä, Nicolas H.},
issn = {0092-8674},
journal = {Cell},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {14},
pages = {3599--3611},
publisher = {Elsevier},
title = {{Reading the chromatinized genome}},
doi = {10.1016/j.cell.2021.05.029},
volume = {184},
year = {2021},
}
@article{15262,
abstract = {The Hunchback (Hb) transcription factor is crucial for anterior-posterior patterning of the Drosophila embryo. The maternal hb mRNA acts as a paradigm for translational regulation due to its repression in the posterior of the embryo. However, little is known about the translatability of zygotically transcribed hb mRNAs. Here, we adapt the SunTag system, developed for imaging translation at single-mRNA resolution in tissue culture cells, to the Drosophila embryo to study the translation dynamics of zygotic hb mRNAs. Using single-molecule imaging in fixed and live embryos, we provide evidence for translational repression of zygotic SunTag-hb mRNAs. Whereas the proportion of SunTag-hb mRNAs translated is initially uniform, translation declines from the anterior over time until it becomes restricted to a posterior band in the expression domain. We discuss how regulated hb mRNA translation may help establish the sharp Hb expression boundary, which is a model for precision and noise during developmental patterning. Overall, our data show how use of the SunTag method on fixed and live embryos is a powerful combination for elucidating spatiotemporal regulation of mRNA translation in Drosophila.},
author = {Vinter, Daisy J. and Hoppe, Caroline and Minchington, Thomas and Sutcliffe, Catherine and Ashe, Hilary L.},
issn = {1477-9129},
journal = {Development},
keywords = {Developmental Biology, Molecular Biology},
number = {18},
publisher = {The Company of Biologists},
title = {{Dynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo}},
doi = {10.1242/dev.196121},
volume = {148},
year = {2021},
}
@article{15272,
abstract = {The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.},
author = {Tang, Leo T. H. and Trivedi, Meera and Freund, Jenna and Salazar, Christopher J. and Rahman, Maisha and Ramirez, Nelson and Lee, Garrett and Wang, Yu and Grant, Barth D. and Bülow, Hannes E.},
issn = {1553-7404},
journal = {PLOS Genetics},
keywords = {Cancer Research, Genetics (clinical), Genetics, Molecular Biology, Ecology, Evolution, Behavior and Systematics},
number = {7},
publisher = {Public Library of Science},
title = {{The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning}},
doi = {10.1371/journal.pgen.1009475},
volume = {17},
year = {2021},
}
@article{15273,
abstract = {Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.},
author = {Balmer, Timothy S and Borges Merjane, Carolina and Trussell, Laurence O},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse}},
doi = {10.7554/elife.63819},
volume = {10},
year = {2021},
}
@article{15276,
abstract = {Biotrophic plant pathogens secrete effector proteins to manipulate the host physiology. Effectors suppress defenses and induce an environment favorable to disease development. Sequence-based prediction of effector function is impeded by their rapid evolution rate. In the maize pathogen Ustilago maydis, effector-coding genes frequently organize in clusters. Here we describe the functional characterization of the pleiades, a cluster of ten effector genes, by analyzing the micro- and macroscopic phenotype of the cluster deletion and expressing these proteins in planta. Deletion of the pleiades leads to strongly impaired virulence and accumulation of reactive oxygen species (ROS) in infected tissue. Eight of the Pleiades suppress the production of ROS upon perception of pathogen associated molecular patterns (PAMPs). Although functionally redundant, the Pleiades target different host components. The paralogs Taygeta1 and Merope1 suppress ROS production in either the cytoplasm or nucleus, respectively. Merope1 targets and promotes the auto-ubiquitination activity of RFI2, a conserved family of E3 ligases that regulates the production of PAMP-triggered ROS burst in plants.},
author = {Navarrete, Fernando and Grujic, Nenad and Stirnberg, Alexandra and Saado, Indira and Aleksza, David and Gallei, Michelle C and Adi, Hazem and Alcântara, André and Khan, Mamoona and Bindics, Janos and Trujillo, Marco and Djamei, Armin},
issn = {1553-7374},
journal = {PLOS Pathogens},
keywords = {Virology, Genetics, Molecular Biology, Immunology, Microbiology, Parasitology},
number = {6},
publisher = {Public Library of Science},
title = {{The Pleiades are a cluster of fungal effectors that inhibit host defenses}},
doi = {10.1371/journal.ppat.1009641},
volume = {17},
year = {2021},
}
@article{10834,
abstract = {Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis.},
author = {Stahnke, Stephanie and Döring, Hermann and Kusch, Charly and de Gorter, David J.J. and Dütting, Sebastian and Guledani, Aleks and Pleines, Irina and Schnoor, Michael and Sixt, Michael K and Geffers, Robert and Rohde, Manfred and Müsken, Mathias and Kage, Frieda and Steffen, Anika and Faix, Jan and Nieswandt, Bernhard and Rottner, Klemens and Stradal, Theresia E.B.},
issn = {0960-9822},
journal = {Current Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {10},
pages = {2051--2064.e8},
publisher = {Elsevier},
title = {{Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion}},
doi = {10.1016/j.cub.2021.02.043},
volume = {31},
year = {2021},
}
@article{11052,
abstract = {In order to combat molecular damage, most cellular proteins undergo rapid turnover. We have previously identified large nuclear protein assemblies that can persist for years in post-mitotic tissues and are subject to age-related decline. Here, we report that mitochondria can be long lived in the mouse brain and reveal that specific mitochondrial proteins have half-lives longer than the average proteome. These mitochondrial long-lived proteins (mitoLLPs) are core components of the electron transport chain (ETC) and display increased longevity in respiratory supercomplexes. We find that COX7C, a mitoLLP that forms a stable contact site between complexes I and IV, is required for complex IV and supercomplex assembly. Remarkably, even upon depletion of COX7C transcripts, ETC function is maintained for days, effectively uncoupling mitochondrial function from ongoing transcription of its mitoLLPs. Our results suggest that modulating protein longevity within the ETC is critical for mitochondrial proteome maintenance and the robustness of mitochondrial function.},
author = {Krishna, Shefali and Arrojo e Drigo, Rafael and Capitanio, Juliana S. and Ramachandra, Ranjan and Ellisman, Mark and HETZER, Martin W},
issn = {1534-5807},
journal = {Developmental Cell},
keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
number = {21},
pages = {P2952--2965.e9},
publisher = {Elsevier},
title = {{Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain}},
doi = {10.1016/j.devcel.2021.10.008},
volume = {56},
year = {2021},
}
@article{10163,
abstract = {The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.},
author = {Appel, Lisa-Marie and Franke, Vedran and Bruno, Melania and Grishkovskaya, Irina and Kasiliauskaite, Aiste and Kaufmann, Tanja and Schoeberl, Ursula E. and Puchinger, Martin G. and Kostrhon, Sebastian and Ebenwaldner, Carmen and Sebesta, Marek and Beltzung, Etienne and Mechtler, Karl and Lin, Gen and Vlasova, Anna and Leeb, Martin and Pavri, Rushad and Stark, Alexander and Akalin, Altuna and Stefl, Richard and Bernecky, Carrie A and Djinovic-Carugo, Kristina and Slade, Dea},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
number = {1},
publisher = {Springer Nature},
title = {{PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC}},
doi = {10.1038/s41467-021-26360-2},
volume = {12},
year = {2021},
}
@article{10301,
abstract = {De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.},
author = {Conde-Dusman, María J and Dey, Partha N and Elía-Zudaire, Óscar and Garcia Rabaneda, Luis E and García-Lira, Carmen and Grand, Teddy and Briz, Victor and Velasco, Eric R and Andero Galí, Raül and Niñerola, Sergio and Barco, Angel and Paoletti, Pierre and Wesseling, John F and Gardoni, Fabrizio and Tavalin, Steven J and Perez-Otaño, Isabel},
issn = {2050-084X},
journal = {eLife},
keywords = {general immunology and microbiology, general biochemistry, genetics and molecular biology, general medicine, general neuroscience},
publisher = {eLife Sciences Publications},
title = {{Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly}},
doi = {10.7554/elife.71575},
volume = {10},
year = {2021},
}
@article{10310,
abstract = {A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.},
author = {Çoruh, Mehmet Orkun and Frank, Anna and Tanaka, Hideaki and Kawamoto, Akihiro and El-Mohsnawy, Eithar and Kato, Takayuki and Namba, Keiichi and Gerle, Christoph and Nowaczyk, Marc M. and Kurisu, Genji},
issn = {2399-3642},
journal = {Communications Biology},
keywords = {general agricultural and biological Sciences, general biochemistry, genetics and molecular biology, medicine (miscellaneous)},
number = {1},
publisher = {Springer },
title = {{Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster}},
doi = {10.1038/s42003-021-01808-9},
volume = {4},
year = {2021},
}
@article{10533,
abstract = {Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin.},
author = {Choi, Jaemyung and Lyons, David B and Zilberman, Daniel},
issn = {2050-084X},
journal = {eLife},
keywords = {genetics and molecular biology},
publisher = {eLife Sciences Publications},
title = {{Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin}},
doi = {10.7554/elife.72676},
volume = {10},
year = {2021},
}
@article{8997,
abstract = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.},
author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias},
issn = {1553-7358},
journal = {PLOS Computational Biology},
keywords = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions},
publisher = {Public Library of Science},
title = {{Minimal biophysical model of combined antibiotic action}},
doi = {10.1371/journal.pcbi.1008529},
volume = {17},
year = {2021},
}
@article{9283,
abstract = {Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.},
author = {Nagy-Staron, Anna A and Tomasek, Kathrin and Caruso Carter, Caroline and Sonnleitner, Elisabeth and Kavcic, Bor and Paixão, Tiago and Guet, Calin C},
issn = {2050-084X},
journal = {eLife},
keywords = {Genetics and Molecular Biology},
publisher = {eLife Sciences Publications},
title = {{Local genetic context shapes the function of a gene regulatory network}},
doi = {10.7554/elife.65993},
volume = {10},
year = {2021},
}
@article{9387,
abstract = {We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift.},
author = {Khudiakova, Kseniia and Neretina, Tatiana Yu. and Kondrashov, Alexey S.},
issn = {0022-5193},
journal = {Journal of Theoretical Biology},
keywords = {General Biochemistry, Genetics and Molecular Biology, Modelling and Simulation, Statistics and Probability, General Immunology and Microbiology, Applied Mathematics, General Agricultural and Biological Sciences, General Medicine},
publisher = {Elsevier },
title = {{Two linked loci under mutation-selection balance and Muller’s ratchet}},
doi = {10.1016/j.jtbi.2021.110729},
volume = {524},
year = {2021},
}
@article{9431,
abstract = {Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.},
author = {Obr, Martin and Ricana, Clifton L. and Nikulin, Nadia and Feathers, Jon-Philip R. and Klanschnig, Marco and Thader, Andreas and Johnson, Marc C. and Vogt, Volker M. and Schur, Florian KM and Dick, Robert A.},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
number = {1},
publisher = {Nature Research},
title = {{Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer}},
doi = {10.1038/s41467-021-23506-0},
volume = {12},
year = {2021},
}
@article{9540,
abstract = {The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.},
author = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Rössler, Ingrid and Klein, Isabella and Hetzmannseder, Christina and Zisser, Gertrude and Gruber, Christian C. and Gruber, Karl and Haselbach, David and Bergler, Helmut},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
number = {1},
publisher = {Springer Nature},
title = {{Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine}},
doi = {10.1038/s41467-021-23854-x},
volume = {12},
year = {2021},
}
@article{9778,
abstract = {The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.},
author = {Vandael, David H and Okamoto, Yuji and Jonas, Peter M},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
number = {1},
publisher = {Springer},
title = {{Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses}},
doi = {10.1038/s41467-021-23153-5},
volume = {12},
year = {2021},
}
@article{8966,
abstract = {During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important prerequisite for the emergence of patterns within the developing organism is to establish asymmetries at various scales, ranging from individual cells to the entire embryo, eventually giving rise to the different body structures. This becomes especially apparent during gastrulation, when the earliest major lineage restriction events lead to the formation of the different germ layers. Traditionally, the unfolding of the developmental program from symmetry breaking to germ layer formation has been studied by dissecting the contributions of different signaling pathways and cellular rearrangements in the in vivo context of intact embryos. Recent efforts, using the intrinsic capacity of embryonic stem cells to self-assemble and generate embryo-like structures de novo, have opened new avenues for understanding the many ways by which an embryo can be built and the influence of extrinsic factors therein. Here, we discuss and compare divergent and conserved strategies leading to germ layer formation in embryos as compared to in vitro systems, their upstream molecular cascades and the role of extrinsic factors in this process.},
author = {Schauer, Alexandra and Heisenberg, Carl-Philipp J},
issn = {0012-1606},
journal = {Developmental Biology},
keywords = {Developmental Biology, Cell Biology, Molecular Biology},
pages = {71--81},
publisher = {Elsevier},
title = {{Reassembling gastrulation}},
doi = {10.1016/j.ydbio.2020.12.014},
volume = {474},
year = {2021},
}
@article{9429,
abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.},
author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Dimchev, Georgi A and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Dotter, Christoph and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Schur, Florian KM and Danzl, Johann G and Novarino, Gaia},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology},
number = {1},
publisher = {Springer Nature},
title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}},
doi = {10.1038/s41467-021-23123-x},
volume = {12},
year = {2021},
}
@article{12189,
abstract = {Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells.},
author = {Christophorou, Nicolas and She, Wenjing and Long, Jincheng and Hurel, Aurélie and Beaubiat, Sébastien and Idir, Yassir and Tagliaro-Jahns, Marina and Chambon, Aurélie and Solier, Victor and Vezon, Daniel and Grelon, Mathilde and Feng, Xiaoqi and Bouché, Nicolas and Mézard, Christine},
issn = {1553-7404},
journal = {PLOS Genetics},
keywords = {Cancer Research, Genetics (clinical), Genetics, Molecular Biology, Ecology, Evolution, Behavior and Systematics},
number = {6},
publisher = {Public Library of Science (PLoS)},
title = {{AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization}},
doi = {10.1371/journal.pgen.1008894},
volume = {16},
year = {2020},
}