Review
Biochemistry & Molecular Biology
Krzysztof Jozwiak, Anita Plazinska
Summary: Studies on different receptors belonging to class A of GPCRs reveal specific molecular mechanisms behind ligand directed signaling, including the role of important residues, the impact of ligand structural features on signaling, and the key interactions between ligands and receptors.
Review
Immunology
Jorge Santos-Lopez, Karla de la Paz, Francisco J. Fernandez, M. Cristina Vega
Summary: The complement system plays vital roles in immune and inflammatory processes and is implicated in various human diseases. Complement receptors regulate complement-mediated immune responses and coordinate innate and adaptive immunity. Understanding the structure of complement factors and their receptor complexes is important for basic and therapeutic research.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Physiology
Jaromir Myslivecek
Summary: Muscarinic receptors, a type of G protein-coupled receptors, have five subtypes. Researchers studying the involvement of mAChRs in various functions need to carefully choose ligands and consider the limited selectivity. This review provides an overview of off-targets, introduces the use of allosteric ligands and biased agonists, and emphasizes the importance of specific experimental designs to avoid ambiguous results.
FRONTIERS IN PHYSIOLOGY
(2022)
Editorial Material
Multidisciplinary Sciences
Hideyuki Takahashi, Stephen M. Strittmatter
Summary: Protein fibrils are known to accumulate in the brain during neurodegeneration, and now cryo-electron microscopy has revealed the high-resolution structures of TMEM106B fibrils, which were not previously thought to accumulate.
Article
Chemistry, Multidisciplinary
Zhipeng A. Wang, Jonathan W. Markert, Samuel D. Whedon, Maheeshi Yapa Abeywardana, Kwangwoon Lee, Hanjie Jiang, Carolay Suarez, Hening Lin, Lucas Farnung, Philip A. Cole
Summary: The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. One member of the HDAC family, Sirt6, efficiently deacetylates several histone H3 acetylation sites on nucleosomes. The structure of Sirt6 bound to a nucleosome reveals its extensive interactions with H2A/H2B acidic patch and nucleosomal DNA, providing insights into how HDACs target and regulate chromatin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Malka Cohen-Armon
Summary: Previous studies suggested that the affinity of seven-transmembrane muscarinic acetylcholine receptors for agonists is influenced by membrane depolarization, but recent reports propose a voltage sensor in the muscarinic receptor. However, experiments measuring acetylcholine binding to muscarinic receptors in brain synaptoneurosomes contradict this explanation. These findings indicate that the voltage-dependent sodium channel (VDSC) acts as the voltage sensor, causing Go-protein activation in response to membrane depolarization, which then modulates the affinity of muscarinic receptors for cholinergic agonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Yasco Aracava, Edson X. Albuquerque, Edna F. R. Pereira
Summary: This study provides the first demonstration that (R,S)trihexyphenidyl (THP) can suppress action potential-dependent synaptic transmission via a mechanism independent of NMDAR, mAChR, and α7 nAChR inhibition.
Review
Plant Sciences
Wen Song, Alexander Forderer, Dongli Yu, Jijie Chai
Summary: Plants use both membrane-bound and intracellular immune receptors to distinguish self from invaders, initiating pattern-triggered immunity and effector-triggered immunity respectively. Pathogens can overcome pattern-triggered immunity by secreting effectors, which are specifically recognized by intracellular NLRs receptors.
Review
Biochemistry & Molecular Biology
Roberta Piovesana, Adam J. Reid, Ada Maria Tata
Summary: The communication between neurons and glial cells has been well-documented in various stages of development and disease. Neurotransmitters, especially acetylcholine, play a significant role in regulating the development and physiology of glial cells. This review focuses on the contribution of neurotransmitter receptors, particularly the M2 muscarinic receptor and the alpha 7 nicotinic receptor, in influencing the phenotype and functioning of Schwann cells. Understanding these interactions can help identify potential therapeutic targets for pathological conditions involving glial cells.
Article
Pharmacology & Pharmacy
Eva Dolejsi, Nikolai Chetverikov, Eszter Szanti-Pinter, Dominik Nelic, Alena Randakova, Vladimir Dolezal, Esam E. El-Fakahany, Eva Kudova, Jan Jakubik
Summary: Endogenous neurosteroids and their synthetic analogues, known as neuroactive steroids, bind to muscarinic acetylcholine receptors and modulate acetylcholine binding and function. Radioligand binding experiments show that neuroactive steroids bind to two different affinity sites on the receptors, with each site having a unique binding profile compared to other allosteric modulators. Additionally, membrane cholesterol competes with neurosteroids/neuroactive steroids binding, indicating that both binding sites are oriented towards the cell membrane.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biology
Chih-Wei Hsu, Juan Cerda, Jason M. Kirk, Williamson D. Turner, Tara L. Rasmussen, Carlos P. Flores Suarez, Mary E. Dickinson, Joshua D. Wythe
Summary: The study introduces a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs without altering sample size and fluorescence signal. The method allows for various imaging modalities while preserving fluorescence signal.
Review
Biochemistry & Molecular Biology
Jaromir Myslivecek
Summary: There are tight interactions between dopamine and acetylcholine signaling in the striatum, affecting neurotransmitter release and movement regulation. Both neurotransmitters and their receptors show diurnal variations, with research indicating that reward function is also influenced by the circadian system.
Article
Chemistry, Medicinal
Marlon Millard, Jonas Kilian, Marius Ozenil, Mariella Mogeritsch, Verena Schwingenschloegl-Maisetschlaeger, Wolfgang Holzer, Marcus Hacker, Thierry Langer, Verena Pichler
Summary: Our research group has identified a new compound as a starting point for designing muscarinic acetylcholine receptor ligands. We have developed promising compounds with favorable drug-like attributes and potential CNS activity. These compounds have the potential for radiolabeling applications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biology
Yaron Caspi, Chrysoula K. Pantazopoulou, Jeanine J. Prompers, Corne M. J. Pieterse, Hilleke Hulshoff Pol, Kaisa Kajala
Summary: Intercellular signalling is essential for multicellular life. Studying the commonalities and differences in how signalling molecules function in different branches of life can provide insights into their recruitment for intercellular signalling. This review focuses on the plant function of three well-studied animal intercellular signalling molecules, glutamate, ?-aminobutyric acid (GABA), and melatonin, and suggests that molecules with key metabolic functions or involvement in reactive ion species scavenging have a high potential for becoming intercellular signalling molecules. Additionally, the evolution of machinery to transduce signals across plasma membranes is necessary, as evidenced by the lack of evidence for serotonin, dopamine, and acetylcholine acting as intercellular signalling molecules in plants.
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Neurosciences
Rebecca L. Kow, Carl Sikkema, Jeanna M. Wheeler, Charles W. Wilkinson, Brian C. Kraemer
BIOLOGICAL PSYCHIATRY
(2018)
Article
Biochemistry & Molecular Biology
Rebecca L. Kow, Jonathan R. Whicher, Claudia A. McDonald, Bruce A. Palfey, Rebecca L. Fagan
Article
Neurosciences
Aaron S. Nudelman, Derek P. DiRocco, Talley J. Lambert, Michael G. Garelick, Josh Le, Neil M. Nathanson, Daniel R. Storm
Article
Biochemistry & Molecular Biology
Neil M. Nathanson
NEUROCHEMISTRY INTERNATIONAL
(2012)
Article
Multidisciplinary Sciences
Cindy L. Reiner, Jennifer S. McCullar, Rebecca L. Kow, Joshua H. Le, David R. Goodlett, Neil M. Nathanson
Article
Multidisciplinary Sciences
Rebecca L. Kow, Kelly Jiang, Alipi V. Naydenov, Joshua H. Le, Nephi Stella, Neil M. Nathanson
Article
Cell Biology
Jeanna M. Wheeler, Pamela McMillan, Timothy J. Strovas, Nicole F. Liachko, Alexandre Amlie-Wolf, Rebecca L. Kow, Ronald L. Klein, Patricia Szot, Linda Robinson, Chris Guthrie, Aleen Saxton, Nicholas M. Kanaan, Murray Raskind, Elaine Peskind, John Q. Trojanowski, Virginia M. Y. Lee, Li-San Wang, C. Dirk Keene, Thomas Bird, Gerard D. Schellenberg, Brian Kraemer
SCIENCE TRANSLATIONAL MEDICINE
(2019)
Article
Neurosciences
Rebecca L. Kow, Timothy J. Strovas, Pamela J. McMillan, Ashley M. Jacobi, Mark A. Behlke, Aleen D. Saxton, Caitlin S. Latimer, C. Dirk Keene, Brian C. Kraemer
Summary: This study demonstrated that simply extending poly(A) tails does not effectively suppress tau-induced pathological accumulation. Instead, a complex relationship was found between tau, sut-2/MSUT2 function, and the control of poly(A) RNA metabolism, with parn-2/TOE1 potentially playing a role in tauopathy in a similar way.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Geriatrics & Gerontology
Rebecca L. Kow, Aristide H. Black, Aleen D. Saxton, Nicole F. Liachko, Brian C. Kraemer
Summary: Loss of ALYREF function can suppress tau and TDP-43-induced toxicity, but with different mechanisms and separate effects on mRNA and protein levels.
Article
Multidisciplinary Sciences
Randall J. Eck, Rebecca L. Kow, Aristide H. Black, Nicole F. Liachko, Brian C. Kraemer
Summary: The pathological accumulation of the microtubule binding protein tau is the main cause of age-related neurodegenerative diseases known as tauopathies. A study using a Caenorhabditis elegans model found that the toxicity of tau depends on the nuclear E3 ubiquitin ligase adaptor protein SPOP. Loss of function mutations in the spop-1 gene improved behavioral deficits in tau transgenic animals, while overexpression of SPOP-1 worsened these deficits. Furthermore, loss of spop-1 rescued various tau-related phenotypes, including tau protein accumulation, neurodegeneration, and shortened lifespan.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
R. L. Kow, A. H. Black, B. P. Henderson, B. C. Kraemer
Summary: This study identifies a mutation (W292X) in the sut-6 gene that strongly suppresses the toxic effects of tau accumulation in neurodegenerative diseases. Altering the RNA-related functions of SUT-6/NIPP1 provides the strongest suppression of tau.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pharmacology & Pharmacy
Rebecca L. Kow, Eugene M. Cheng, Kelly Jiang, Joshua H. Le, Nephi Stella, Neil M. Nathanson
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2015)
