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Translocator protein and neurodegeneration: insights from Alzheimer’s disease

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Neural Regeneration Research 2025年第4期20卷 1090-1091页

作者： Arpit Kumar Pradhan Rainer Rupprecht Gerhard Rammes Klinik für Anaesthesiologie und Intensivmedizin der Technischen Universität München Klinikum rechts der IsarMunichGermany Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität MünchenMartinsriedGermany Department of Psychiatry and Psychotherapy University RegensburgRegensburgGermany

The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce *** main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.

关键词： cholesterol organs

Take-over:multiple mechanisms of inter-adipocyte communication

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分子细胞生物学报:英文版 2011年第2期3卷 81-90页

作者： Gunter Muller Department Biology I Genetics MartinsriedBiocenterLudwig-Maximilians-University MunichMunichGermany

Adipose tissue mass in mammals is thought to expand with an increase in both volume and total number of the *** findings suggest that in normal-weight as well as obese individuals,the adipocyte number is set during adolescence prior to adulthood,whereas the subsequent increase in size predominantly drives *** simultaneous existence of large and small adipocytes and their unsynchronized growth,even within the same adipose tissue depot,argues against simple filling-up of emerging adipocytes with lipids and lipid droplets(LDs).Consequently,it is tempting to speculate about signals sent by large adipocytes to order small adipocytes the take-over of the burden of lipid *** there is experimental evidence for three distinct types of inter-adipocyte signals,***-to-cell contacts,adipokines,and other soluble factors and *** recently,microvesicles have been shown(i)to harbour the glycosylphosphatidylinositol-anchored(c)AMP-degrading phosphodiesterase Gce1 and 5′-nucleotidase CD73,(ii)to be released from large adipocytes,(iii)to interact with small adipocytes,and(iv)to transfer Gce1 and CD73 to plasma membranes and LDs of small adipocytes where they degrade(c)*** sequence of events leads to the up-regulation of lipid storage in small adipocytes in response to the microvesicle-encoded‘take-over’signal from large adipocytes.A model is proposed for the maturation of small adipocytes driven by large ones along a gradient of those inter-adipocyte *** modulation of inter-adipocyte communication and thereby adipocyte maturation may be useful for the therapy of metabolic diseases.

关键词： adipokines fat cells glycosylphosphatidylinositol lipid droplets lipid metabolism microvesicles obesity type 2 diabetes

Secondary neurogenesis and telencephalic organization in zebrafish and mice: a brief review

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Integrative Zoology 2009年第1期4卷 123-133页

作者： Mario F.WULLIMANN Department of Biology II Ludwig-Maximilians-UniversityMunich-MartinsriedGermany

Most zebrafish neurodevelopmental studies have focused on the embryo,which is characterized by primary neurogenesis of mostly transient *** neurogenesis becomes dominant in the hatching larva,when major brain parts are established and begin to *** developmental period allows for a comparative analysis of zebrafish brain organization with amniotes at equivalent stages of *** a particular time window,the early forebrains of mice(Embyronic stage[E]12.5/13.5 days[d])and zebrafish(3 d)reveal highly comparable expression patterns of genes involved in neurogenesis,for example proneural and other transcription factors(Neurogenin1,NeuroD,Mash1/Zash1a and Pax6).Further topological correspondences are seen in the expression of LIM and homeobox genes,such as Lhx6/7,Tbr2 and *** this analysis is extended to gamma-aminobutyric acid/glutamic acid decarboxylase(GABA/GAD)cell patterns during this critical time window,an astonishing degree of similarity between the two species is again seen,for example regarding the presence of GABA/GAD cells in the subpallium,with the pallium only starting to be invaded by such cells from the ***,the expression of proneural and other genes correlates with GABA cell patterns(***1/Zash1a gene expression in GABA-positive and Neurogenin1/NeuroD in GABA-negative telencephalic regions)in mice and *** from additional vertebrates,such as Xenopus,are also highly consistent with this ***,the vertebrate forebrain appears to undergo a phylotypic stage of secondary neurogenesis,characterized by regionally separated GABAergic(inhibitory)versus glutamatergic(excitatory)cell production sites,which are obscured later in development by tangential *** period is highly advantageous for molecular neuroanatomical cross-species comparisons.

关键词： basal ganglia cortex subpallium tangential migration gamma-aminobutyric acid GABA.

The role of epigenetic inactivation of 14-3-3σ in human cancer

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Cell Research 2005年第4期15卷 237-246页

作者： Dmitri LODYGIN, Heiko HERMEKING Molecular Oncology Max-Planck Institute of Biochemistry Am Klopferspitz 18 martinsried/munich Germany Molecular Oncology Max-Planck Institute of Biochemistry Am Klopferspitz 18 martinsried/munich Germany

Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor *** studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.

关键词： 14-3-3σ CpG methylation p53 epigenetic silencing cancer cell cycle.

Enhancing the light reactions of photosynthesis:Strategies,controversies,and perspectives

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Molecular Plant 2023年第1期16卷 4-22页

作者： Dario Leister Plant Molecular Biology Faculty of BiologyLudwig-Maximilians-University(LMU)MunichMartinsried-PlaneggD-82152 MunichGermany

Photosynthesis is central to life on Earth,employing sunlight,water,and carbon dioxide to produce chemical energy and *** is generally accepted that boosting its efficiency offers one promising way to increase crop yields under agronomically realistic *** the components,structure,and regulatory mechanisms of the light reactions of photosynthesis are well understood,concepts for enhancing the process have been suggested and partially *** approaches vary in complexity,from targeting single components to comprehensive redesign of the whole process on the scales from single cells or tissues to whole *** to enhance light utilization per leaf,by decreasing pigmentation,increasing levels of photosynthetic proteins,prolonging the lifespan of the photosynthetic machinery,or massive reconfiguration of the photosynthetic machinery and the incorporation of nanomaterials,are discussed in this review ***,strategies intended to optimize the acclimation of photosynthesis to changes in the environment are presented,including redesigning mechanisms to dissipate excess excitation energy(e.g.,non-photochemical quenching)or reduction power(e.g.,flavodiiron proteins).Moreover,schemes for improving acclimation,inspired by natural or laboratory-induced adaptation,are ***,all these endeavors are still in an early exploratory phase and/or have not resulted in the desired outcome,largely because photosynthesis is embedded within large networks of closely interacting cellular and metabolic processes,which can vary among species and even *** explains why integrated,systems-wide approaches are required to achieve the breakthroughs required for effectively increasing crop yields.

关键词： Arabidopsis adaptive laboratory evolution crop yield photosynthesis synthetic biology tobacco

Arabidopsis OBG-Like GTPase （AtOBGL）Is Localized in Chloroplasts and Has an Essential Function in Embryo Development

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Molecular Plant 2009年第6期2卷 1373-1383页

作者： Fatima Chigri Claudia Sippel Manuela Kolb Ute C. Vothknecht Center for Integrated Protein Science (munich) Department of Biology LMU Munich D-81377 Munich Germany Department of Biology I Botany LMU Munich D-82152 Planegg-Martinsried Germany

OBG-like GTPases, a subfamily of P-loop GTPases, have divers and important functions in bacteria, including initiation of sporulation, DNA replication, and protein translation. Homologs of the Bacillus subtilis spo0B GTP-binding protein （OBG） can be found in plants and algae but their specific function in these organisms has not yet been elucidated. Here, it is shown that ATSG18570 encodes an Arabidopsis thaliana OBG-like protein （AtOBGL） that is localized in chlor- oplasts. In contrast to the bacterial members of this protein family, AtOBGL and other OBG-like proteins from green algae and plants possess an additional N-terminal domain, indicating functional adaptation. Disruption of the gene locus of ATOBGL by TDNA insertion resulted in an embryo-lethal phenotype and light microscopy using Normarski optics revealed that embryo maturation in the atobgl mutant is arrested at the late globular stage before development of a green embryo. Expression of 35S：：ATOBGL within the atobgl mutant background could rescue the mutant phenotype, confirming that embryo-lethality is caused by the loss of AtOBGL. Together, the data show that the bacterial-derived OBG-like GTPases have retained an essential role in chloroplasts of plants and algae. They furthermore corroborate the significance of chloroplast functions for embryo development -- an important stage within the Arabidopsis lifecycle.

关键词： GTPase OBG embryo development chloroplast.

COG1-A master transcription factor regulating photosynthesis

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Molecular Plant 2023年第12期16卷 1890-1892页

作者： Jan Ferdinand Penzler Tatjana Kleine Dario Leister Plant Molecular Biology Faculty of BiologyLudwig-Maximilians-University(LMU)MunichMartinsried-Planegg82152 MunichGermany

COG1 CANENHANCE PHOTOSYNTHESIS AND PLANT GROWTH Recently,Wei et al.(2023)report that overexpression or a gain-offunction mutation of COGWHEEL1(COG1)gene,which encodes a transcription factor belonging to the DNA binding with one finger(Dof)protein family,can increase growth and biomass in Arabidopsis ***,overexpression of any of its six paralogs,CYCLING DOF FACTORS 1-6,also leads to increased growth and biomass production,implying that these seven Dof proteins have partially redundant ***,several of the seven Dof genes must be knocked out to significantly reduce growth and biomass production;the septuple mutants show severely reduced growth but are still ***1 positively modulates the accumulation of transcripts of several photosynthetic genes and,in turn,the corresponding proteins and binds to the promoters of most LHC *** in gene expression related to photosynthesis increase the efficiency of *** of two closely related Brassica rapa COG1 homologs in *** or Arabidopsis COG1 in Nicotiana benthamiana,could cause an increase in growth and biomass *** results indicate that the effects of COG1 are not confined to a specific species.

关键词： species. functions. Arabidopsis

Redox Regulation of Arabidopsis Mitochondrial Citrate Synthase

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Molecular Plant 2014年第1期7卷 156-169页

作者： Elisabeth Schmidtmann Ann-Christine Konig Anne Orwat Dario Leister Markus Hartl Iris Finkemeier Botany Department I of Biology Ludwig-Maximilians-University Munich Grosshaderner Strasse 2 82152 Planegg-Martinsried Germany

Citrate synthase has a key role in the tricarboxylic （TCA） cycle of mitochondria of all organisms, as it cata- lyzes the first committed step which is the fusion of a carbon-carbon bond between oxaloacetate and acetyl CoA. The regulation of TCA cycle function is especially important in plants, since mitochondrial activities have to be coordinated with photosynthesis. The posttranslational regulation of TCA cycle activity in plants is thus far almost entirely unexplored. Although several TCA cycle enzymes have been identified as thioredoxin targets in vitro, the existence of any thioredoxin-dependent regulation as known for the Calvin cycle, yet remains to be demonstrated. Here we have investigated the redox regulation of the Arabidopsis citrate synthase enzyme by site-directed mutagenesis of its six cysteine residues. Our results indicate that oxidation inhibits the enzyme activity by the formation of mixed disulfides, as the partially oxidized citrate synthase enzyme forms large redox-dependent aggregates. Furthermore, we were able to demonstrate that thioredoxin can cleave diverse intraas well as intermolecular disulfide bridges, which strongly enhances the activity of the enzyme. Activity measurements with the cysteine variants of the enzyme revealed important cysteine residues affecting total enzyme activity as well as the redox sensitivity of the enzyme.

关键词： citrate synthase mitochondria cysteine residues redox regulation thioredoxin TCA cycle Arabidopsis.

Zinc Fingers, TAL Effectors, or Cas9-Based DNA Binding Proteins： What＇s Best for Targeting Desired Genome Loci？

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Molecular Plant 2013年第5期6卷 1384-1387页

作者： Annett Strauβ Thomas Lahaye Faculty of Biology Institute of Genetics Ludwig-Maximilians-University Munich Grolβhaderner Straβe 2-4 D-82152 Martinsried Germany

ZINC FINGER- AND TAL EFFECTOR- BASED DNA BINDING PROTEINSProgrammable DNA binding proteins （PDPs） that selectively bind user-defined nucleotide sequences can navigate protein domains to any desired target within the genome. Different functional domains can be fused to PDPs to achieve （1） acti- vation or repression of transcription, （2） nicking or cleavage of DNA, or （3） modification or removal of epigenetic marks at the targeted genome spot. Given their broad applicabil- ity, the development of highly specific, easy-to-use PDPs has been a holy grail of biotechnology since the determination of the 3-D structure of zinc fingers （ZFs） bound to DNA in 1991 （Pavletich and Pabo, 1991）. This structure suggested that tandemly arranged ZFs act as functionally independ- ent modules with each finger binding three bases. However, the combination of fingers with experimentally defined base specificities into arrays revealed that ZFs are not function- ally independent. Instead, they were found to behave in a context-dependent, and often unpredictable fashion requir- ing iterative cycles of selection to get ZF arrays with desired specificity （Joung and Sander, 2013）.

关键词： DNA结合蛋白基因组 TAL 锌指期望基础蛋白质结构域用户自定义