Article
Biochemistry & Molecular Biology
Hitomi Nakao, Akira Seko, Yukishige Ito, Masafumi Sakono
Summary: This study found that the endoplasmic reticulum protein ERp29 may act as a bridge linking the lectin chaperones calnexin and calreticulin, forming complexes such as CNX-CRT. This not only facilitates the binding of CNX and CRT, but also reveals a new function of ERp29.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ryosuke Inoue, Yosuke Fukutani, Tatsuya Niwa, Hiroaki Matsunami, Masafumi Yohda
Summary: Olfactory receptors (ORs) in olfactory sensory neurons mediate olfaction and require the assistance of receptor-transporting proteins (RTPs) for functional expression. This study examined the interactome of RTP1S and OR using proximity biotinylation and revealed the involvement of HSPA6 and STAU2 in the trafficking process of OR through interaction with RTP1S.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nicolas Bloemeke, Kevin Meighen-Berger, Manuel Hitzenberger, Nina C. Bach, Marina Parr, Joao Pl Coelho, Dmitrij Frishman, Martin Zacharias, Stephan A. Sieber, Matthias J. Feige
Summary: One-third of the human proteome is composed of membrane proteins, which are susceptible to misfolding and require folding assistance from chaperones. Calnexin, an abundant ER chaperone, interacts with a large number of membrane proteins, including misfolded ones, using its lectin domain and transmembrane domain for recognition and binding. This study reveals the widespread role of calnexin in recognizing client proteins in the lipid bilayer and highlights its importance in supporting membrane protein biogenesis.
Article
Biochemistry & Molecular Biology
Amanda B. Abildgaard, Vasileios Voutsinos, Soren D. Petersen, Fia B. Larsen, Caroline Kampmeyer, Kristoffer E. Johansson, Amelie Stein, Tommer Ravid, Claes Andreasson, Michael K. Jensen, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and chaperone-binding regions may function as PQC degrons. A canonical Hsp70-binding motif, the APPY peptide, functions as a dose-dependent PQC degron in yeast and human cells. The number of exposed Hsp70-binding sites in the yeast proteome correlates with reduced protein abundance and half-life.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Eszter Zavodszky, Sew-Yeu Peak-Chew, Szymon Juszkiewicz, Ana J. Narvaez, Ramanujan S. Hegde
Summary: In eukaryotic cells, excess PSMC5, a subunit of the proteasome base, is targeted for degradation by the HERC1 ubiquitin ligase. HERC1 recognizes unassembled PSMC5 with the help of its assembly chaperone PAAF1 and can also engage in the degradation of later assembly intermediates such as the PSMC4-PSMC5-PAAF1 complex. A missense mutant of HERC1 impairs the recognition and ubiquitination of the PSMC5-PAAFI complex, indicating that proteasome assembly factors can serve as adaptors for ubiquitin ligases to eliminate unassembled intermediates and maintain protein homeostasis.
Review
Biochemistry & Molecular Biology
Kristen Schroeder, Kristina Jonas
Summary: The asymmetric life cycle of Caulobacter crescentus serves as a model for studying how protein quality control networks interact with cell cycle and developmental processes. The organism's response to stress conditions enables it to prevent, revert, and remove protein damage.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Shinya Ito, Kazuhiro Nagata
Summary: Collagen, the most abundant protein in mammals, has a unique triple-helical structure formed by Gly-Xaa-Yaa repeats, crucial for its functions such as bone strength and signal transduction. The quality control of collagen biosynthesis in the endoplasmic reticulum is maintained by heat shock protein 47, mutations affecting this process can lead to collagen destabilization and degradation.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Engineering, Civil
Ruicheng Lu, Minghui Ma, Shidong Liang
Summary: Variable speed limit (VSL) strategies have been proven to be effective in mitigating traffic congestion at freeway bottlenecks. In this paper, a dynamic cycle strategy of VSL based on predictive control is developed, which includes an analysis of applicable situations, a probability model for cycle selection, and the use of a transmission model to predict traffic flow. An optimization algorithm is also designed to optimize the cycle and speed limit options. Simulation results demonstrate that the proposed strategies and algorithms can effectively reduce traffic congestion and improve the service level of freeway networks.
TRANSPORTATION RESEARCH RECORD
(2023)
Article
Biochemistry & Molecular Biology
Pei-Wen Chen, Anjelika Gasilina, Mukesh P. Yadav, Paul A. Randazzo
Summary: ADP-ribosylation factors (Arfs) are a family of regulatory GTP binding proteins that primarily regulate membrane trafficking and cytoskeleton remodeling. In addition, Arfs have been found to play a role in signaling and integrating multiple signaling pathways to influence specific cell behaviors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Medicine, General & Internal
Wei Wang, Lingjuan Xu, Guanyu Su, Ban Luo, Jing Gao, Yongyao Tan, Hong Zhang, Guigang Li
Summary: This study measured the thickness of the corneal endothelium-Descemet membrane (EDM) layer in patients with Descemet membrane detachment (DMD) using high-definition optical coherence tomography (HD-OCT), and found that the EDM thickness was correlated with age. The detachment time did not affect the EDM thickness, and there was a difference in EDM thickness between corneas with and without DMD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ssu-Ju Fu, Meng-Chun Hu, Cheng-Tsung Hsiao, An-Ting Cheng, Tsung-Yu Chen, Chung-Jiuan Jeng, Chih-Yung Tang
Summary: The ClC-2 channel is crucial for ion homeostasis in the brain and testis, with mutations in the CLCN2 gene linked to leukodystrophy. Clcn2-deficient mice exhibit myelin vacuolation and testicular degeneration. The Hsp90 beta-Hsc70 chaperone system plays a key role in promoting ClC-2 protein biogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Civil
Hong Wang, Sagar Patil, H. M. Abdul Aziz, Stanley Young
Summary: This work focuses on using stochastic distribution control theory to optimize traffic signal timing and achieve smooth and uniform flow of vehicles at signalized intersections. Two stochastic distribution control algorithms are designed to minimize the probability density function of traffic queues at each intersection. A data-driven and dynamic recursive input-output traffic queue estimation model is proposed to calculate real-time queue lengths. Simulations demonstrate the effectiveness of the algorithms compared to commonly used semi-actuated control.
IEEE TRANSACTIONS ON INTELLIGENT TRANSPORTATION SYSTEMS
(2022)
Article
Biochemistry & Molecular Biology
Yoshihiko Miyata, Eisuke Nishida
Summary: The DYRK family comprises five related protein kinases, with DYRK1A linked to disorders such as Down syndrome. It was found that Hsp90 and Cdc37 are specific cellular protein chaperones for DYRK1B and DYRK4, playing a crucial role in quality control of these kinases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Neurosciences
Stacy L. Hrizo, Samantha L. Eicher, Tracey D. Myers, Ian McGrath, Andrew P. K. Wodrich, Hemanth Venkatesh, Daniel Manjooran, Sabrina Swoger, Kim Gagnon, Matthew Bruskin, Maria V. Lebedev, Sherry Zheng, Ana Vitantonio, Sungyoun Kim, Zachary J. Lamb, Andreas Vogt, Maura R. Z. Ruzhnikov, Michael J. Palladino
Summary: Triosephosphate isomerase (TPI) deficiency is a rare metabolic disorder characterized by reduced TPI protein stability and potential co-translational selection for polyubiquitination. A genome-wide RNAi screen targeting quality control proteins identified novel regulators of TPI(sugarkill) degradation, uncovering potential therapeutic pathways for TPI Df and other diseases.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Chemistry, Multidisciplinary
Ana B. Caballero, Patrick Gamez
Summary: The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, primarily neurodegenerative diseases. Recent findings suggest that impairment in proteostasis network may lead to accumulation and spread of amyloids, contributing to a new focus in anti-amyloid drug design. Chaperones, as known regulators of proteostasis, represent interesting targets for the development of novel therapeutics, with the concept of nanochaperone potentially leading towards the development of cost-effective, disease-modifying drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Peter J. Minogue, Jun-Jie Tong, Kelly Wichmann, Hubert Mysliwiec, Lisa Ebihara, Eric C. Beyer, Viviana M. Berthoud
Summary: This study found that two serine mutants, Cx50S258F and Cx50S259Y, linked to cataracts exhibit abnormal intercellular coupling in the lens, whereas alanine substitution mutants, Cx50S258D and Cx50S259D, can increase the abundance and size of intercellular coupling. In addition, the protein levels of serine mutants Cx50S258F and Cx50S259Y are lower, and lysosome is involved in their degradation. The presence of a sorting signal and phosphorylation sites can affect the targeting and stabilization of Cx50, thus impacting the function of the lens.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rachel Morgan, Candela Manfredi, Kristen F. Easley, Lionel D. Watkins, William R. Hunt, Steven L. Goudy, Eric J. Sorscher, Michael Koval, Samuel A. Molina
Summary: This study successfully differentiated human basal cells isolated from the nasal and conducting airway into mature epithelial cells at the air-liquid interface (ALI) using a medium with normal resting glucose levels, avoiding the need for high glucose concentrations. The use of normal glucose-containing ALI medium also enabled differentiation of nasal and tracheal cells and allowed for long-term cell responsiveness.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Joanna Gemel, Jared Zhang, Yifan Mao, Gabrielle Lapping-Carr, Eric C. Beyer
Summary: The study found that extracellular vesicles (EVs) in the plasma of patients with sickle cell disease (SCD) disrupt the integrity of endothelial cell monolayers, especially during episodes of acute chest syndrome (ACS). The findings suggest that circulating EVs may be involved in modulating endothelial integrity and contributing to the pathogenesis of different complications of SCD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Peter J. Minogue, Andre J. Sommer, James C. Williams, Sharon B. Bledsoe, Eric C. Beyer, Viviana M. Berthoud
Summary: Cataracts, a common cause of blindness, are believed to develop from accumulation of damage to lens proteins. However, recent evidence suggests that calcium ion accumulation and precipitation of calcium-containing salts may also lead to cataracts. Studies on mutant mice with cataracts caused by connexin46 and connexin50 mutations found the presence of radio-dense minerals in the mutant lenses, suggesting a pathological mineralization process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
John D. Lyons, Pratyusha Mandal, Shunsuke Otani, Deena B. Chihade, Kristen F. Easley, David A. Swift, Eileen M. Burd, Zhe Liang, Michael Koval, Edward S. Mocarski, Craig M. Coopersmith
Summary: Deletion or mutation of RIPK3 reduces inflammation and mortality in mice with Pseudomonas pneumonia. RIPK3 kinase activity is dispensable for cell killing but is involved in cytokine production. The RIPK3 scaffold domain mediates deleterious inflammation and may be a target for reducing lung inflammation during infection.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Editorial Material
Physiology
Eric C. Beyer, Viviana M. Berthoud, Julie C. Lim, Paul J. Donaldson
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Physiology
Eric C. Beyer, Richard T. Mathias, Viviana M. Berthoud
Summary: The lens circulation and intercellular coupling play important roles in the development of various types of cataracts and connexin mutations are a common cause. However, aging leads to decreased intercellular coupling and connexin levels, resulting in disruption of ionic homeostasis.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Oscar Jara, Peter J. Minogue, Viviana M. Berthoud, Eric C. Beyer
Summary: The study explored the roles of connexin46 and 50 in the mouse lens, finding that mutations in connexins can lead to cataracts and investigating the relationship between mutant and wild-type connexins. The results suggest that there are complex interactions between these two connexin proteins expressed in the same cell.
Article
Peripheral Vascular Disease
Luke. S. Dunaway, Marie Billaud, Edgar Macal, Miranda. E. Good, Christopher. B. Medina, Ulrike Lorenz, Kodi Ravichandran, Michael Koval, Brant. E. Isakson
Summary: This study suggests that Panx1 in smooth muscle cells plays a role in regulating sympathetic nerve constriction and blood pressure. The findings also demonstrate the feasibility of using Panx1-mouse models to test potential drugs for hypertension.
Article
Biochemistry & Molecular Biology
Abhishek Bose, Grishma Kasle, Rishika Jana, Mahua Maulik, Deepthi Thomas, Vaishali Mulchandani, Priyanka Mukherjee, Michael Koval, Jayasri Das Sarma
Summary: Gap junctional intercellular communication involving astrocytes is essential for CNS homeostasis. Infection with MHV-A59 disrupts the trafficking of Cx43, the main GJ protein in astrocytes, but the underlying mechanism is not clear. In this study, we found that retention of Cx43 due to MHV-A59 infection is associated with increased ER stress and reduced expression of chaperone protein ERp29. Treatment with a chemical chaperone rescues Cx43 transport, increases GJIC, and reduces ER stress. These findings provide insights into a therapeutically targetable mechanism where ERp29 modulates beta-coronavirus infectivity by alleviating ER stress and restoring Cx43 trafficking.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Critical Care Medicine
Deena B. Chihade, Prestina Smith, David A. Swift, Shunsuke Otani, Wenxiao Zhang, Ching-Wen Chen, Lauren A. Jeffers, Zhe Liang, Takashi Shimazui, Eileen M. Burd, Alton B. Farris, Bashar S. Staitieh, David M. Guidot, Mandy L. Ford, Michael Koval, Craig M. Coopersmith
Summary: Increased permeability in sepsis is mediated by disruptions in tight junctions, and genetic deletion of myosin light chain kinase (MLCK) reverses this effect in intra-abdominal sepsis. However, in this study, MLCK deletion unexpectedly increased mortality in pneumonia-induced sepsis, associated with worsened alveolar epithelial leak and systemic inflammation. These findings caution against targeting MLCK for therapeutic gain in sepsis.
Article
Pharmacology & Pharmacy
Michael Koval, Wyatt J. Schug, Brant E. Isakson
Summary: Pannexin channels have important roles in regulating inflammation and are associated with various diseases. Blocking these channels pharmacologically is crucial for therapeutic approaches. This review discusses the current state of agents that can block pannexin channels, focusing on pharmaceuticals and peptide mimetics targeting pannexin 1. It also provides guidance on interpreting results obtained with pannexin pharmacologics and evaluates the strengths and limitations of different agents in terms of specificity and clinical application.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Anastasia Kolousek, Ezra Pak-Harvey, Oliver Liu-Lam, Mia White, Prestina Smith, Fernanda Henning, Michael Koval, Joshua M. Levy
Summary: The endocannabinoid system is a potential therapeutic target for chronic inflammatory disease, including respiratory illnesses. This scoping review explores the impact of endocannabinoid activity on eicosanoid production and its role in airway inflammation. The findings suggest that endocannabinoid activation can increase COX-2 expression and lead to increased levels of prostaglandin E-2.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Substance Abuse
Viranuj Sueblinvong, Xian Fan, Craishun Hart, Samuel Molina, Michael Koval, David M. Guidot
Summary: Chronic alcohol ingestion induces dysregulated TGF beta 1 and GM-CSF in lung fibroblasts, leading to impaired airway epithelial barrier function. Co-culturing ethanol-exposed lung fibroblasts with airway epithelial cells resulted in decreased transepithelial electrical resistance, reduced expression of tight junction protein ZO-1, and increased expression of collagen type 1A1 and α-smooth muscle actin. These effects were mediated through the activation of TGF beta 1 signaling and suppression of GM-CSF, and could be prevented by blocking TGF beta 1 activity.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Biology
Samuel A. Molina, Daniela Maier-Begandt, Brant E. Isakson, Michael Koval
Summary: The permeability of blood vessels is regulated by endothelial cells. This permeability is influenced by factors such as the type of blood vessel and the specific disease state. Most studies on endothelial permeability have been conducted using isolated cells in culture, which may not accurately reflect the native cell environment. In this study, the authors describe a method that allows for the measurement of endothelial properties in intact blood vessels, providing a more accurate analysis of the response to various stresses in the context of the intact vessel.