Daniela C Dieterich's research while affiliated with Otto-von-Guericke-Universität Magdeburg and other places

Publications (98)

Article
Astrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region‐specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an inducible Aldh1l1‐methionyl‐tRNA‐synthetaseL274G (MetRSL274G) mou...
Preprint
Astrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region-specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an Aldh1l1-MetRSL274G mouse line that allows cell-type specific labe...
Article
Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...
Article
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Influenza A virus (IAV) causes respiratory tract disease and is responsible for seasonal and reoccurring epidemics affecting all age groups. Next to typical disease symptoms, such as fever and fatigue, IAV infection has been associated with behavioral alterations presumably contributing to the development of major depression. Previous experiments u...
Preprint
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Influenza A virus (IAV) causes respiratory tract disease and is responsible for seasonal and reoccurring epidemics affecting all age groups. Next to typical disease symptoms such as fever and fatigue, IAV infection has been associated with behavioral alterations presumably contributing to the development of major depression. Previous experiments us...
Article
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Cell survival and function critically relies on the fine-tuned balance of protein synthesis and degradation. In the steady state, the standard proteasome is sufficient to maintain this proteostasis. However, upon inflammation, the sharp increase in protein production requires additional mechanisms to limit protein-associated cellular stress. Under...
Article
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The immunological synapse is a transient junction that occurs when the plasma membrane of a T cell comes in close contact with an antigen‐presenting cell after recognizing a peptide from the antigen‐major histocompatibility complex. The interaction starts when CRAC channels embedded in the T cell membrane open, flowing calcium ions into the cell. T...
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Relief learning is the association of environmental cues with the cessation of aversive events. While there is increasing knowledge about the neural circuitry mediating relief learning, the respective molecular pathways are not known. Therefore, the aim of the present study was to examine different putative molecular pathways underlying relief lear...
Article
Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about...
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Proteolysis as mediated by one of the major cellular protein degradation pathways, the ubiquitin–proteasome system (UPS), plays an essential role in learning and memory formation. However, the functional relevance of immunoproteasomes in the healthy brain and especially their impact on normal brain function including processes of learning and memor...
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Copper-catalyzed azide-alkyne-cycloaddition (CuAAC), also known as 'click chemistry' serves as a technique for bio-orthogonal, that is, bio-compatible labeling of macromolecules including proteins or lipids. Click chemistry has been widely used to covalently, selectively, and efficiently attach probes such as fluorophores or biotin to small bio-ort...
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Deoxynivalenol (DON) is a toxin found in cereals as well as in processed products such as pasta, and causes substantial economic losses for stock breeding as it induces vomiting, reduced feeding, and reduced growth rates in piglets. Oxidative phosphorylation, TCA-cycle, transcription, and translation have been hypothesized to be leading pathways th...
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Although advances in protein labeling methods have made it possible to measure the proteome of mixed cell populations, it has not been possible to isolate cell-type-specific proteomes in vivo. This is because the existing methods for metabolic protein labeling in vivo access all cell types. We report the development of a transgenic mouse line where...
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Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic e...
Article
Advanced mass spectrometry technology has pushed proteomic analyses to the forefront of biological and biomedical research. Limitations of proteomic approaches now often remain with sample preparations rather than with the sensitivity of protein detection. However, deciphering proteomes and their context-dependent dynamics in subgroups of tissue-em...
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Axonal branching and terminal arborization are fundamental events during the establishment of synaptic connectivity. They are triggered by assembly of actin filaments along axon shafts giving rise to filopodia. The specific contribution of the three actin isoforms, Actα, Actβ, and Actγ, to filopodia stability and dynamics during this process is not...
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The molecular synaptic mechanisms underlying auditory learning and memory remain largely unknown. Here, the workflow of a proteomic study on auditory discrimination learning in mice is described. In this learning paradigm, mice are trained in a shuttle box Go/NoGo-task to discriminate between rising and falling frequency-modulated tones in order to...
Article
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K2P5.1 channels (also called TASK-2 or KCNK5) have already been shown to be relevant in the pathophysiology of autoimmune disease since they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P5.1 channels in vitro provokes enhanced T-cell effector functions. Howeve...
Chapter
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The first reports on tolerance to the serotonergic hallucinogen lysergic acid diethylamide (LSD) were published half a century ago, yet hitherto, a systematic review on this topic is not available. In this chapter, we discuss tolerance to LSD with regard to its psychedelic and somatic effects in humans, as well as selected behaviors in animals. In...
Article
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Learning and memory processes are accompanied by rearrangements of synaptic protein networks. While various studies have demonstrated the regulation of individual synaptic proteins during these processes, much less is known about the complex regulation of synaptic proteomes. Recently, we reported that auditory discrimination learning in mice is ass...
Article
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Extracts of Asparagus cochinchinensis (AC) have antitumor, anti-inflammatory, and immunostimulant effects. The neurobiological mechanisms underlying the effects of AC have not been sufficiently explored. Thus we performed in vivo and in vitro experiments to further characterize potential therapeutic effects and to clarify the underlying mechanisms....
Article
Taste information is processed in different brain structures in the mammalian brain, including the gustatory cortex (GC), which resides within the insular cortex. N-methyl-D-aspartate receptor (NMDAR) activity in the GC is necessary for the acquisition of conditioned taste aversion (CTA) but not positive novel taste learning. Previous studies have...
Data
Original images of Immunoblotting. (A) Original immunoblots related to Fig 1B. (B) Original immunoblots related to Fig 3B. The layer with the protein ladder was omitted in the main figure. (C) Original immunoblots related to Fig 3D. The layer with the protein ladder was omitted in the main figure. (D) Original immunoblots related to Fig 6A. The lay...
Data
The methionine binding pocket of MetRS is highly conserved among species. (A) Whereas AHA is sterically similar to methionine and can be processes by the endogenous methionyl-tRNA synthetase, the side chain of ANL is longer and, therefore, excluded by the wild type enzyme. (B) The Met binding pocket is highly conserved and sequences are comparable...
Data
Example of Cx43 quantification in the Golgi apparatus of astrocytes. Neuron-glia cocultures (DIV 22) were infected with LVGFAPEGFP and treated with 50 ng/ml BDNF for 4 h. Cx43 positive signals were observed in the Golgi apparatus of astrocytes applying immunocytochemistry for Cx43 and the Golgi marker GM130. Cx43 signal intensities are color coded...
Data
Successful ANL integration into de novo synthesized proteins by BONCAT. Primary neuron-glia cocultures (DIV 21), either infected with LVGFAPEGFP-mMetRSL274G or not treated, were incubated with either 4 mM AHA, ANL or Met for 4 h. Successful ANL integration into proteins was detected with a biotin-alkyne tag using ‘click-reaction’ of cell lysates, f...
Data
Analysis of cell death and protein degradation proves a vital culture after ANL integration. (A) HEK293T cells were transfected with either the EGFP-mMetRSwt or the mutant enzyme version EGFP-mMetRSL274G and incubated for 4 h with 4 mM ANL or Met in Met-free medium. A live-staining with a 2 μg/ml propidium iodide solution revealed a slight tendency...
Article
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The ability of the nervous system to undergo long-term plasticity is based on changes in cellular and synaptic proteomes. While many studies have explored dynamic alterations in neuronal proteomes during plasticity, there has been less attention paid to the astrocytic counterpart. Indeed, progress in identifying cell type-specific proteomes is limi...
Data
Cell type-specific labeling with ANL in a neuron-glia coculture. Primary neuron-glia cocultures (DIV 22), infected with the lentivirus LVGFAPEGFP-mMetRSL274G, expressed the enzyme cell type-specific in astrocytes. Cells were incubated with either 4 mM AHA, ANL or Met for 4 h in Met-free medium and AHA or ANL incorporation was visualized by a TAMRA-...
Article
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Using auditory discrimination learning in gerbils, we have previously shown that activation of auditory-cortical D1/D5 dopamine receptors facilitates mTOR-mediated, protein synthesis-dependent mechanisms of memory consolidation and anterograde memory formation. To understand molecular mechanisms of this facilitatory effect, we tested the impact of...
Article
Neuronal as well as glial cells contribute to higher order brain functions. Many observations show that neurons and glial cells are not only physically highly intermingled but are physiologically tightly connected and mutually depend at various levels on each other. Moreover, macroglia classes like astrocytes, NG2 cells and oligodendrocytes are not...
Article
Zusammenfassung Sowohl neuronale als auch gliale Zellen tragen zu höheren Hirnfunktionen bei. Viele Beobachtungen zeigen, dass Neurone und Gliazellen nicht nur physische Berührungspunkte besitzen, sondern auch physiologisch eng verbunden sind und auf vielen Ebenen wechselseitig voneinander abhängen. Zudem stellen Macroglia wie Astrozyten, NG2 - Zel...
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The advances in mass-spectrometry based proteomics in the past 15 years have contributed to a deeper appreciation of protein networks and the composition of functional synaptic protein complexes. However, research on protein dynamics underlying core mechanisms of synaptic plasticity in brain lag far behind. In this review we provide a synopsis on p...
Article
Dissecting the regional diversity of glial cells by applying - omic technologies. Neuronal as well as glial cells contribute to higher order brain functions. Many observations show that neurons and glial cells are notionly physically highly intermingled but are physiologically tightly connected and mutually depend at various levels on each other. M...
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The specification and adaptability of cells rely on changes in protein composition. Nonetheless, uncovering proteome dynamics with cell-type-specific resolution remains challenging. Here we introduce a strategy for cell-specific analysis of newly synthesized proteomes by combining targeted expression of a mutated methionyl-tRNA synthetase (MetRS) w...
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Dominant mutations in five tRNA synthetases cause Charcot-Marie-Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS)....
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Metabolic labeling of proteins using classical radioisotope-labeled amino acids has enabled the analysis and function of protein synthesis for many biological processes but cannot be combined with modern high-throughput mass spectrometry analysis. This chapter describes the unbiased identification of a whole de novo synthesized proteome of cultured...
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Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate wh...
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Background/aims: The trefoil factor family (TFF) peptide TFF3 is typically secreted by mucous epithelia, but is also expressed in the immune system and the brain. It was the aim of this study to determine the cerebral cell types which express Tff3. Methods: Primary cultures from rat embryonic or neonatal cerebral cortex and hippocampus, respecti...
Article
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The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and l...
Data
Distributions of metabolic half-life estimates of proteins selected according to particular GO annotations. Subsets of proteins were selected according to specific GO annotations and distributions of their metabolic half-life estimates were compared to those of the entire population (2,804 proteins). A) Cell compartment: “Synapse” (105 proteins). B...
Data
Distribution of sum of square errors (SSE) for fits to single exponentials. SSE values for all identified proteins for which data was obtained for all four time points (2,859 proteins). The lower the SSE value, the better the fit. Note that the fit for the vast majority of proteins was excellent (SSE <0.02) and only a very small number of proteins...
Data
Quantification of synaptic densities at the four time points of the SILAC experiments. Cortical neurons were grown on glass bottom substrates for two weeks in an identical fashion to preparations used for SILAC experiments. The neurons were then fixed after an additional 0, 1, 3 or 7 days and stained against the PSD molecule PSD-95. Nine Z sections...
Data
Comparison of MS profiles of labeled and unlabeled samples. Cortical neurons were either grown in the presence of 6× heavy AAs for 3 days (starting at day 14 in vitro as described in main text and in Materials and Methods) or maintained in standard growth media for the same period (control). Lysates of these preparations were then subjected to MS a...
Data
Effects of an excess of heavy AA on network activity. Cortical neurons were grown on multielectrode (MEA) substrates for two weeks in an identical fashion to preparations used for SILAC experiments. The preparations were then mounted on an MEA amplifier as described previously [33]. Spontaneous activity was measured for 3 hours after which heavy AA...
Data
Distributions of metabolic half-life estimates obtained by “conventional” dynamic SILAC. Neurons were grown for 2 weeks in lysine and arginine-free MEM to which Lys8 and Arg10 were added at nominal concentrations. After two weeks, cells were washed and placed in conditioned media from “sister” preparations (see Materials and Methods for details). 0...
Data
Fractional intensity of synaptic proteins in SILAC experiments. The intensity measured for all peptides (H+L) for all synaptic proteins, divided by the intensities measured for all identified proteins. As equal amounts of proteins were loaded on the separation gels, these data indicate that the fraction of synaptic proteins in the protein mixture b...
Article
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Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on...
Data
List of 2,802 proteins for which satisfactory metabolic half-life estimates were obtained. List was sorted according to half-life estimate value (color coded). Only proteins for which SILAC data was obtained for all 4 time points, and for which fits to single exponentials were acceptable are included in this list. As the data was pooled from multip...
Data
Repeatability of half-life estimations. A) Distributions of half-life estimates obtained separately in two experiments carried out two weeks apart. Only proteins for which data from all 4 time points was obtained in both experiments were included (1,622 proteins). B) Comparison of half-life estimates for individual proteins (1,608). Proteins with h...
Data
Comparison of fractional incorporation ratios for neurons maintained in culture for 2 weeks and 3 weeks. Cortical neurons were maintained in culture for either 2 weeks or 3 weeks and then exposed to heavy AA for 3 days as described in main text and in Materials and Methods. Lysates of these preparations were then subjected to MS analysis as describ...
Article
Here we demonstrate quantitation of stimuli-induced proteome dynamics in primary cells by combining the power of bio-orthogonal noncanonical amino acid tagging (BONCAT) and stable-isotope labeling of amino acids in cell culture (SILAC). In conjunction with nanoscale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), quantitative noncano...
Article
Fluorescent labeling of proteins by genetically encoded fluorescent protein tags has enabled an enhanced understanding of cell biological processes but is restricted to the analysis of a limited number of identified proteins. This approach does not permit, e.g., the unbiased visualization of a full proteome in situ. We describe here a fluorescence-...
Article
Local protein synthesis and its activity-dependent modulation via dopamine receptor stimulation play an important role in synaptic plasticity - allowing synapses to respond dynamically to changes in their activity patterns. We describe here the metabolic labeling, enrichment, and MS-based identification of candidate proteins specifically translated...
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Chemical synapses are highly specialized cell-cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ) organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsy...