Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Jessica A. Lawrence, Patricia Aguilar-Calvo, Daniel Ojeda-Juarez, Helen Khuu, Katrin Soldau, Donald P. Pizzo, Jin Wang, Adela Malik, Timothy F. Shay, Erin E. Sullivan, Brent Aulston, Seung Min Song, Julia A. Callender, Henry Sanchez, Michael D. Geschwind, Subhojit Roy, Robert A. Rissman, JoAnn Trejo, Nobuyuki Tanaka, Chengbiao Wu, Xu Chen, Gentry N. Patrick, Christina J. Sigurdson
Summary: Endolysosomal defects, including the reduction of Hrs and STAM1, exacerbate synaptic derangements and accelerate neurodegeneration in prion-infected brains. Depletion of neuronal Hrs leads to increased surface levels of PrPC, contributing to the rapidly advancing disease through neurotoxic signaling. The findings highlight the importance of proteostatic pathways and synaptic integrity in prion diseases.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Anna M. Lenkiewicz, Magda Krakowczyk, Piotr Bragoszewski
Summary: The synthesis and targeting of mitochondrial proteins are essential processes for maintaining mitochondrial function and cell survival. The cytosolic protein homeostasis mechanism and the ubiquitin-proteasome system play critical roles in controlling the quality and supply of mitochondrial proteins. Mislocalization of mitochondrial proteins can contribute to disease development. Pathways involved in precursor maintenance and guidance in the cytosolic stages are crucial for restoring protein homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Clinical Neurology
Jordan J. S. VerPlank, Joseph Gawron, Nicholas J. Silvestri, M. Laura Feltri, Lawrence Wrabetz, Alfred L. Goldberg
Summary: Agents that raise cGMP levels can increase proteasome activity and degrade misfolded proteins, potentially providing therapeutic benefits for neurodegenerative diseases and conditions caused by protein accumulation.
Review
Biochemistry & Molecular Biology
Taylor Thomas, David Salcedo-Tacuma, David M. Smith
Summary: This review discusses the regulation of proteasomes, with a focus on the unique characteristics of the 11S, REGs, or PA26/PA28 family of regulators. The evolution and cellular biology of these regulators are explored, and their structure and function are comprehensively compared, highlighting unanswered questions regarding their regulatory mechanisms and broader roles in proteostasis.
Article
Biochemistry & Molecular Biology
Shanshan Xu, Maria E. Gierisch, Anna Katharina Schellhaus, Ina Poser, Simon Alberti, Florian A. Salomons, Nico P. Dantuma
Summary: The absence of stress granules in cells has a negative impact on the functionality of the nuclear ubiquitin-proteasome system (UPS). Defective ribosome products (DRiPs) in stress granule-deficient cells accumulated at nucleoli instead of stress granules, accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4 restored the functionality of the nuclear UPS in stress granule-deficient cells. Stress granule-deficient cells showed increased formation of mutant ataxin-1 nuclear inclusions under thermal stress. These findings highlight the importance of stress granules in sequestering cytosolic misfolded proteins and preventing their accumulation in the nucleus.
Review
Biochemistry & Molecular Biology
David C. Hughes, Leslie M. Baehr, David S. Waddell, Adam P. Sharples, Sue C. Bodine
Summary: The development and prevalence of diseases associated with aging have a global health burden on society. One hallmark of aging is the loss of proteostasis, partly caused by alterations to the ubiquitin-proteasome system and lysosome-autophagy system, leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In skeletal muscle, functional impairment occurs early in the aging process and depends on proteostatic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Carolyn Allain Breckel, Mark Hochstrasser
Summary: The proper folding of proteins is vital for their diverse functions, and misfolded proteins can potentially harm cells by forming aggregates. Protein quality control pathways are responsible for repairing or degrading abnormal proteins, with the ubiquitin-proteasome system being commonly employed.
Article
Biochemistry & Molecular Biology
Sean M. Cascarina, Joshua P. Kaplan, Mikaela R. Elder, Lindsey Brookbank, Eric D. Ross
Summary: The degradation sensitivity of G-rich and Q/N-rich domains is influenced by specific sequence features, with G-rich domains being more susceptible to degradation-promoting effects of hydrophobic residues. The proteostasis network may act as a selection mechanism at the molecular level, constraining the sequence space accessible to G-rich domains. However, the sensitivity or resistance of these domains is not always preserved in their native protein contexts, indicating the complexity of protein evolution in overcoming degradation susceptibility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Gonca cetin, Sandro Klafack, Maja Studencka-Turski, Elke Kruger, Frederic Ebstein
Summary: The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in cells, particularly impacting immune cells and their rapid functional remodeling during immune activation. Recent research has shed light on the molecular mechanisms by which UPS contributes to immune responses and its role in immune disorders like cancer and auto-inflammatory diseases.
Article
Oncology
Ka-Yiu Edwin Kong, Joao P. L. Coelho, Matthias J. Feige, Anton Khmelinskii
Summary: A healthy and functional proteome is crucial for cell physiology, but errors in protein metabolism and changes in the environment can disrupt proteome homeostasis. Mislocalized and orphan proteins can form due to targeting errors or improper assembly, impacting cellular functions. Quality control mechanisms play a role in minimizing the detrimental effects of these aberrant proteins, which are associated with aging and disease.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Gayatree Mohapatra, Avital Eisenberg-Lerner, Yifat Merbl
Summary: The gut epithelial barrier is the first line of defense in protecting the internal environment from external influences, requiring rapid and efficient responses to challenges like pathogenic infections and commensal bacteria. Proteolysis plays a crucial role in maintaining gut homeostasis and adapting to environmental changes. The ubiquitin-proteasome system tightly regulates inflammatory signaling and protein quality control in the gut, preventing proteotoxic damage accumulation and contributing to rapid responses.
Review
Cell Biology
Danielle Cozachenco, Felipe C. Ribeiro, Sergio T. Ferreira
Summary: The homeostasis of cellular proteins, or proteostasis, is crucial for neuronal function and brain processes, including learning and memory. Defective proteostasis has been found to contribute to the progression of Alzheimer's disease, the most common form of dementia in the elderly. This article discusses the molecular pathways involved in protein synthesis and degradation that are altered in Alzheimer's disease, as well as potential pharmacological approaches to correct these defects.
AGEING RESEARCH REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Hangjun Sun, Xinxin Jing, Chaonan Wang, Pengyue Wang, Ziting Huang, Bingjian Sun, Pengbai Li, Honglian Li, Chao Zhang
Summary: Plant viruses cause significant damage to global crop production and plants activate defense signaling pathways to hinder virus propagation. Protein homeostasis regulation plays a vital role in the ongoing battle between plants and viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela Anni, Eva-Maria Weiss, Debarpan Guhathakurta, Yagiz Enes Akdas, Julia Klueva, Stefanie Zeitler, Maria Andres-Alonso, Tobias Huth, Anna Fejtova
Summary: The study shows that Aβ 1-42 and Aβ 1-16 can increase the size of the recycling pool of synaptic vesicles, driven by enhanced endogenous cholinergic signaling.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Miriam Ryl, Alexander Urbasik, Kaspar Gierke, Norbert Babai, Anneka Joachimsthaler, Andreas Feigenspan, Renato Frischknecht, Nina Stallwitz, Anna Fejtova, Jan Kremers, Julia von Wittgenstein, Johann Helmut Brandstaetter
Summary: The study investigated the impact of mutations in the Bassoon protein on the synaptic function and structure of photoreceptor cells in mice. Results showed that the synaptic defects were more severe in Bsn(gt/gt) mice, while expression of the Bsn(gt) allele led to cone photoreceptor death and neurite sprouting in the outer retina.
Article
Biochemistry & Molecular Biology
Liubov S. Kalinichenko, Christiane Muehle, Tianye Jia, Felix Anderheiden, Maria Datz, Anna-Lisa Eberle, Volker Eulenburg, Jonas Granzow, Martin Hofer, Julia Hohenschild, Sabine E. Huber, Stefanie Kaempf, Georgios Kogias, Laura Lacatusu, Charlotte Lugmair, Stephen Mbu Taku, Doris Meixner, Nina Tesch, Marc Praetner, Cosima Rhein, Christina Sauer, Jessica Scholz, Franziska Ulrich, Florian Valenta, Esther Weigand, Markus Werner, Nicole Tay, Conor J. Mc Veigh, Jana Haase, An-Li Wang, Laila Abdel-Hafiz, Joseph P. Huston, Irena Smaga, Malgorzata Frankowska, Malgorzata Filip, Anbarasu Lourdusamy, Philipp Kirchner, Arif B. Ekici, Lena M. Marx, Neeraja Puliparambil Suresh, Renato Frischknecht, Anna Fejtova, Essa M. Saied, Christoph Arenz, Aline Bozec, Isabel Wank, Silke Kreitz, Andreas Hess, Tobias Baeuerle, Maria Dolores Ledesma, Daniel N. Mitroi, Andre M. Miranda, Tiago G. Oliveira, Erich Gulbins, Bernd Lenz, Gunter Schumann, Johannes Kornhuber, Christian P. Muller
Summary: Mental disorders and physical diseases often coincide, with a study identifying an enzyme that regulates alcohol consumption and emotional behavior, affecting the interaction between the brain and bones to impact the development of these conditions.
MOLECULAR PSYCHIATRY
(2021)
Article
Neurosciences
Tina Ghelani, Carolina Montenegro-Venegas, Anna Fejtova, Thomas Dresbach
Summary: Bassoon acts as a core scaffold protein in the presynaptic active zone, with its N-terminus oriented towards the trans-Golgi network membrane and its C-terminus facing away from the trans-Golgi network. This topographic arrangement at the Golgi-apparatus is essential for the assembly of active zone precursor structures and provides insights into the biogenesis of active zones.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Liubov S. Kalinichenko, Christiane Muehle, Tianye Jia, Felix Anderheiden, Maria Datz, Anna-Lisa Eberle, Volker Eulenburg, Jonas Granzow, Martin Hofer, Julia Hohenschild, Sabine E. Huber, Stefanie Kaempf, Georgios Kogias, Laura Lacatusu, Charlotte Lugmair, Stephen Mbu Taku, Doris Meixner, Nina-Kristin Sembritzki, Marc Praetner, Cosima Rhein, Christina Sauer, Jessica Scholz, Franziska Ulrich, Florian Valenta, Esther Weigand, Markus Werner, Nicole Tay, Conor J. Mc Veigh, Jana Haase, An-Li Wang, Laila Abdel-Hafiz, Joseph P. Huston, Irena Smaga, Malgorzata Frankowska, Malgorzata Filip, Anbarasu Lourdusamy, Philipp Kirchner, Arif B. Ekici, Lena M. Marx, Neeraja Puliparambil Suresh, Renato Frischknecht, Anna Fejtova, Essa M. Saied, Christoph Arenz, Aline Bozec, Isabel Wank, Silke Kreitz, Andreas Hess, Tobias Bauerle, Maria Dolores Ledesma, Daniel N. Mitroi, Andre M. Miranda, Tiago Gil Oliveira, Bernd Lenz, Gunter Schumann, Johannes Kornhuber, Christian P. Mueller
Summary: The use, abuse, and addiction of alcohol and the resulting health risks are highly dependent on sex, with unknown mechanisms. This study found that the SMPD3 gene and its protein NSM play a role in alcohol abuse, emotional behavior, and bone defects, with different mechanisms in females and males.
Article
Biochemistry & Molecular Biology
Laura Cherchi, Daniela Anni, Mario Buffelli, Marco Cambiaghi
Summary: The study found that cathodal transcranial direct current stimulation (C-tDCS) applied 6 hours after ischemia could improve motor function of the affected forelimb and decrease microglial cell density in the area surrounding the ischemic core. The modified microglia morphology may contribute to motor recovery.
Article
Clinical Neurology
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Sean J. McAteer, Rebecca E. Milton, Georgina F. Osborne, Edward J. Smith, Samuel T. Jones, Marie K. Bondulich, Emily C. E. Danby, Jemima Phillips, Bridget A. Taxy, Holly B. Kordasiewicz, Gillian P. Bates
Summary: Fienko et al. show that alternative processing of human huntingtin (HTT) mRNA to generate HTT1a occurs in YAC128 mice, which has implications for the design of huntingtin-lowering therapies.
Article
Biochemistry & Molecular Biology
Carolina Montenegro-Venegas, Debarpan Guhathakurta, Eneko Pina-Fernandez, Maria Andres-Alonso, Florian Plattner, Eckart D. Gundelfinger, Anna Fejtova
Summary: This study reveals that the protein bassoon organizes the release of neurotransmitters by regulating synaptic phosphorylation and cAMP homeostasis. Synapses lacking bassoon exhibit decreased release competence of synaptic vesicles and increased resting pool of vesicles. Furthermore, the CDK5/PDE4/cAMP signaling pathway plays a crucial role in the regulation of neurotransmitter release.
Article
Cell & Tissue Engineering
Enes Yagiz Akdas, Soeren Turan, Debarpan Guhathakurta, Arif Ekici, Seda Salar, D. Chichung Lie, Beate Winner, Anna Fejtova
Summary: C-terminal Binding Protein 1 (CTBP1) is a regulatory protein involved in transcription and membrane trafficking. A specific mutation in CTBP1, c.991C>T, leads to the development of HADDTS, a rare neurodevelopmental disorder. In this study, hESCs with this mutation were generated using CRISPR/Cas9 genome editing, providing valuable tools for investigating HADDTS pathophysiology and potential therapeutics.
STEM CELL RESEARCH
(2023)
Editorial Material
Cell Biology
Saeideh Nakhaei-Rad, Anna Fejtova
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Mathematical & Computational Biology
Debarpan Guhathakurta, Enes Yagiz Akdas, Anna Fejtova, Eva-Maria Weiss
Summary: The recent development of cellular imaging techniques and genetically encoded sensors has greatly improved neurobiological studies. In this study, a MATLAB-based segmentation algorithm called SynEdgeWs was developed to efficiently detect and analyze fluorescently labeled synaptic puncta. The algorithm showed superior performance compared to other methods and required minimal user intervention. The application of SynEdgeWs in two automatized routines allowed for accurate and unbiased identification of synaptic puncta in three-channel images and image stacks. The feasibility of the algorithm was tested using live-cell imaging data and proved to be effective in analyzing neurotransmitter release. Overall, SynEdgeWs provides a valuable tool for the analysis of complex and large datasets in neurobiological studies.
FRONTIERS IN BIOINFORMATICS
(2022)