Article
Biochemistry & Molecular Biology
Andrew G. Manford, Elijah L. Mena, Karen Y. Shih, Christine L. Gee, Rachael McMinimy, Brenda Martinez-Gonzalez, Rumi Sherriff, Brandon Lew, Madeline Zoltek, Fernando Rodriguez-Perez, Makda Woldesenbet, John Kuriyan, Michael Rape
Summary: Oxidative phosphorylation not only produces ATP, but also generates reactive oxygen species. Cells alleviate reductive stress by ubiquitylating and degrading FNIP1, which relies on zinc as a molecular glue during this process.
Article
Biochemistry & Molecular Biology
Peng Jiang, Lejiao Ren, Li Zhi, Zhong Yu, Fengxiang Lv, Fengli Xu, Wei Peng, Xiaoyu Bai, Kunlun Cheng, Li Quan, Xiuqin Zhang, Xianhua Wang, Yan Zhang, Dan Yang, Xinli Hu, Rui-Ping Xiao
Summary: High glucose suppresses AMPK signaling through MG53-mediated AMPK alpha degradation and deactivation, as well as ROS-dependent inhibition of AMPK alpha phosphorylation at T172. These findings elucidate the mechanism of impaired AMPK signaling in overnutrition-related diseases and underscore the importance of maintaining the yin-yang balance of AMPK signaling for metabolic homeostasis.
Editorial Material
Plant Sciences
Yusheng Zhao, Zhiyong Liu
Summary: Zhang et al. (2023) demonstrated through association analysis that the wheat E3 ubiquitin ligase TaAIRP2-1B positively regulates spike length by involving an upstream regulator, TaERF3, and a downstream target, TaHIPP3. This study provides a deeper understanding of spike architecture regulation and offers an alternative molecular module for designing wheat with increased yield potential.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Cell Biology
Emanuela Senatore, Rosa Iannucci, Francesco Chiuso, Rossella Delle Donne, Laura Rinaldi, Antonio Feliciello
Summary: Primary cilia are microtubule-based sensory organelles that receive and transmit external signals to control cell growth, differentiation, and development. The formation and disassembly of primary cilia are finely regulated during the cell cycle. The ubiquitin-proteasome system and autophagy machinery play essential roles in cilia dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Debdeep Dutta, Vartika Sharma, Mousumi Mutsuddi, Ashim Mukherjee
Summary: Notch signaling is an evolutionarily conserved pathway widely used for multiple cellular events during development. The pathway is tightly regulated by physical and biochemical modifications of the Notch receptor and its ligand, as well as through the process of ubiquitination carried out by E3 ubiquitin ligases to maintain proper signaling outcomes. Dysregulation of ubiquitination in Notch signaling can lead to abnormal signaling and contribute to various human diseases.
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Multidisciplinary Sciences
Catarina Dias, Erisa Nita, Jakub Faktor, Ailish C. Tynan, Lenka Hernychova, Borivoj Vojtesek, Jesper Nylandsted, Ted R. Hupp, Tilo Kunath, Kathryn L. Ball
Summary: CHIP, an E3-ubiquitin ligase, plays a crucial role in healthy aging and neuroprotection. A study on patient-derived human neuronal model revealed that loss of CHIP function primarily affects a focused group of proteins related to actin cytoskeleton signaling and membrane integrity networks. Knockout cells without CHIP showed increased sensitivity to induced membrane damage, indicating that modulation of substrates involved in maintaining cellular health contributes to the neuroprotective functions of CHIP.
Article
Biochemistry & Molecular Biology
Matthew C. J. Yip, Samantha F. Sedor, Sichen Shao
Summary: This study reveals that ubiquitin binding and a cofactor, NAP1L1, regulate the selection of protein quality-control clients by the hybrid E2/E3 enzyme UBE2O. Attaching a single ubiquitin onto a client enhances UBE2O binding and multi-mono-ubiquitylation. UBE2O also repurposes the histone chaperone NAP1L1 as an adapter to recruit a subset of clients. Cryo-EM structures of human UBE2O in complex with NAP1L1 reveal a malleable client recruitment interface that is autoinhibited by the intrinsically reactive UBC domain. Adding a ubiquitylated client identifies a distinct ubiquitin-binding SH3-like domain required for client selection. Our findings highlight how multivalency and a feed-forward mechanism drive the selection of protein quality-control clients.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Peng Wang, Chao-Tao Tang, Jun Li, Xia Huang, Ruiri Jin, Fang Yin, Zide Liu, Youxiang Chen, Chunyan Zeng
Summary: This study investigated the regulatory role of RNF31 in NLRP3 inflammasome activation during the development of ulcerative colitis (UC). The results showed that RNF31 could interact with NLRP3 and increase its stability through increased ubiquitination. The knockdown of RNF31 effectively reduced inflammation in a mouse model of UC, indicating the potential therapeutic importance of RNF31-mediated regulation of NLRP3.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biology
Sara Scinicariello, Adrian Soderholm, Markus Schaefer, Alexandra Shulkina, Irene Schwartz, Kathrin Hacker, Rebeca Gogova, Robert Kalis, Kimon Froussios, Valentina Budroni, Annika Bestehorn, Tim Clausen, Pavel Kovarik, Johannes Zuber, Gijs A. Versteeg
Summary: Tristetraprolin (TTP) stability is controlled by factors including lysine-ubiquitination and phosphorylation. The E3 ligase HUWE1 was identified as a regulator of TTP stability, indirectly controlling its phosphorylation. This study provides new insights into the regulation of TTP and its impact on immune response.
Article
Physiology
Gustavo R. Ares
Summary: This study found that cGMP mediates the ubiquitination of NKCC2 through the cullin-RING E3 ubiquitin ligase complex, thus regulating surface NKCC2 levels and reducing the reabsorption of sodium chloride. This finding provides new targets for the regulation of NKCC2 expression and activity.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hans-Wolfgang Klafki, Oliver Wirths, Brit Mollenhauer, Thomas Liepold, Petra Rieper, Hermann Esselmann, Jonathan Vogelgsang, Jens Wiltfang, Olaf Jahn
Summary: Neurochemical biomarkers can aid in the diagnosis of Alzheimer's disease, and the A beta-3-40/A beta 1-42 ratio in blood plasma can accurately predict cerebral amyloid-beta pathology. The presence of A beta-3-40 and A beta-3-38 in human cerebrospinal fluid has been confirmed, and the ratio of CSF A beta-3-40/A beta 42 appears to be increased in individuals with amyloid-beta PET-positive results.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Roberto Feuda, Anant K. Menon, Martin C. Goepfert
Summary: Opsins, the protein components of animal visual photo-pigments, have been identified as moonlighting proteins with diverse physiological functions both dependent and independent of light. This highlights the need for revising basic assumptions regarding opsin expression, structure, classification, and evolution.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Neurosciences
Max S. Farnworth, Gregor Bucher, Volker Hartenstein
Summary: Insect brains are formed by conserved sets of neural lineages with cohesive bundles of fibers and characteristic projection patterns. The overall architecture of the neuropils and macrocircuitry is conserved, but variations in size, shape, and timing of development can occur. The developmental and genetic basis of this variation is poorly understood, but the use of genetically tractable model organisms like Tribolium castaneum allows for potential mechanistic insights. This study presents an atlas of the developing brain of T. castaneum, providing a comparison with Drosophila melanogaster and confirming a high degree of conservation. The findings highlight differences between the two species in terms of neuron proliferation and maturation timing, likely reflecting adaptive changes in brain development from larvae to adults.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Martin Meschkat, Anna M. Steyer, Marie-Theres Weil, Kathrin Kusch, Olaf Jahn, Lars Piepkorn, Paola Aguei-Gonzalez, Nhu Thi Ngoc Phan, Torben Ruhwedel, Boguslawa Sadowski, Silvio O. Rizzoli, Hauke B. Werner, Hannelore Ehrenreich, Klaus-Armin Nave, Wiebke Moebius
Summary: This study reveals the importance of continuous incorporation of new myelin membranes in maintaining the integrity of axon-myelin units. Experimental prevention of new myelin formation resulted in degradation of existing myelin, leading to thinning of myelin and shortening of internodes, ultimately affecting the function of myelin and axons.
NATURE COMMUNICATIONS
(2022)
Article
Behavioral Sciences
Vranda Garg, Selina Andre, Diego Giraldo, Luisa Heyer, Martin C. Goepfert, Roland Dosch, Bart R. H. Geurten
Summary: The accurate detection of animal positions and pose is essential for analyzing kinematics, locomotion, and spatial tasks. Most available trackers represent animals as single points in space or use markers to build a skeletal representation of pose. LACE is a marker-free pose-estimator that builds the pose of the animal de novo from its contour, providing a versatile method for assessing position, pose, and movement patterns even in animals without limbs.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Biology
Tobias J. Buscham, Maria A. Eichel-Vogel, Anna M. Steyer, Olaf Jahn, Nicola Strenzke, Rakshit Dardawal, Tor R. Memhave, Sophie B. Siems, Christina Muller, Martin Meschkat, Ting Sun, Torben Ruhwedel, Wiebke Mobius, Eva-Maria Kramer-Albers, Susann Boretius, Klaus-Armin Nave, Hauke B. Werner, Kelly Monk
Summary: CMTM5 plays a role in maintaining axonal integrity rather than myelin biogenesis, as its deficiency leads to early-onset progressive axonopathy without affecting the development or ultrastructure of myelin.
Article
Biology
Vasiliki-Ilya Gargareta, Josefine Reuschenbach, Sophie B. Siems, Ting Sun, Lars Piepkorn, Carolina Mangana, Erik Spate, Sandra Goebbels, Inge Huitinga, Wiebke Moebius, Klaus-Armin Nave, Olaf Jahn, Hauke B. Werner
Summary: By using quantitative proteomics, the comparative analysis of myelin proteins in human and mouse models reveals species-dependent diversity, providing important insights for translating findings from mouse models to humans.
Article
Agronomy
Christian Spalthoff, Vincent L. Salgado, Mario Theis, Bart R. H. Geurten, Martin C. Goepfert
Summary: The selective aphicide flonicamid has been found to affect the femoral chordotonal organ in locusts and disrupt the transduction and mechanical amplification in antennal chordotonal neurons in fruit flies. Its major metabolite, 4-trifluoromethylnicotinamide (TFNA-AM), also stimulates chordotonal organs in both locusts and flies. These effects are similar to those of TRPV agonists pymetrozine, pyrifluquinazon, and afidopyropen.
PEST MANAGEMENT SCIENCE
(2022)
Editorial Material
Multidisciplinary Sciences
Max S. Farnworth, Stephen H. Montgomery
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Madhuvanthi Kannan, Ganesh Vasan, Simon Haziza, Cheng Huang, Radoslaw Chrapkiewcz, Junjie Luo, Jessica A. Cardin, Mark J. Schnitzer, Vincent A. Pieribone
Article
Multidisciplinary Sciences
Tim Duking, Lena Spieth, Stefan A. Berghoff, Lars Piepkorn, Annika M. Schmidke, Miso Mitkovski, Nirmal Kannaiyan, Leon Hosang, Patricia Scholz, Ali H. Shaib, Lennart Schneider, Dorte Hesse, Torben Ruhwedel, Ting Sun, Lisa Linhoff, Andrea Trevisiol, Susanne Koehler, Adrian Marti Pastor, Thomas Misgeld, Michael Sereda, Imam Hassouna, Moritz J. Rossner, Francesca Odoardi, Till Ischebeck, Livia de Hoz, Johannes Hirrlinger, Olaf Jahn, Gesine Saher
Summary: This study provides insights into the energy metabolism of different brain cell types in response to altered nutrition and neurological disease, highlighting the importance of metabolic cross-talk between CNS cells and between the periphery and the brain.
Article
Biochemical Research Methods
Thomas Liepold, Hans-Wolfgang Klafki, Sathish Kumar, Jochen Walter, Oliver Wirths, Jens Wiltfang, Olaf Jahn
Summary: Amyloid-fi (Afi) peptides, including modified variants, are believed to be involved in Alzheimer's disease. However, previous studies relied on antibody-based approaches, and further analyses are needed to verify the existence of phosphorylated Afi species in brain samples using mass spectrometry. A customized matrix formulation called TOPAC was developed to improve the detection of synthetic phosphorylated Afi species. TOPAC showed higher signal intensities and minimal oxidation and loss for intact and proteolytic cleavage products, making it a valuable tool for detecting and characterizing phosphorylated Afi species in biological samples.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Neurosciences
Hans-Wolfgang Klafki, Barbara Morgado, Oliver Wirths, Olaf Jahn, Chris Bauer, Hermann Esselmann, Johannes Schuchhardt, Jens Wiltfang
Summary: Our findings suggest that the relatively small difference in the plasma A beta 42/40 ratio between subjects with and without evidence of brain amyloidosis can be accentuated by specifically measuring A beta 1-42/1-40 instead of A beta X-42/X-40.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Clinical Neurology
Madhurima Chatterjee, Selcuk Oezdemir, Marcel Kunadt, Marleen Koel-Simmelink, Walter Boiten, Lars Piepkorn, Thang V. Pham, Davide Chiasserini, Sander R. Piersma, Jaco C. Knol, Wiebke Moebius, Brit Mollenhauer, Wiesje M. van der Flier, Connie R. Jimenez, Charlotte E. Teunissen, Olaf Jahn, Anja Schneider
Summary: This study aims to comprehensively characterize the proteome of cerebrospinal fluid (CSF) extracellular vesicles (EVs) to identify proteins and pathways altered in Alzheimer's disease (AD). By screening and detecting protein expression, more than 30 differentially expressed proteins involved in immune-regulation were found in AD EVs. The results suggest that EVs may serve as potential biomarkers for AD and play an unprecedented role in immune regulation.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biology
Angelika Sabine Bader, Marius-Uwe Gnaedig, Merle Fricke, Luca Bueschgens, Lena Josefine Berger, Hans-Wolfgang Klafki, Thomas Meyer, Olaf Jahn, Sascha Weggen, Oliver Wirths
Summary: Senile plaques consisting of amyloid-beta (A beta) peptides are a major pathological hallmark of Alzheimer's disease (AD). A beta 1-40 and A beta 1-42 are considered canonical full-length A beta species. In 5XFAD mice, overall plaque load increased in the subiculum, hippocampus, and cortex, with the subiculum having the highest plaque coverage. The load of A beta 1-x peaked at five months and decreased thereafter in the subiculum, while plaques positive for truncated A beta 4-x species increased continuously over time. We hypothesize ongoing plaque remodeling leads to conversion of A beta 1-x peptides into A beta 4-x peptides in brain regions with high A beta plaque burden.
