Article
Neurosciences
Grant P. Higerd-Rusli, Matthew Alsaloum, Sidharth Tyagi, Nivedita Sarveswaran, Mark Estacion, Elizabeth J. Akin, Fadia B. Dib-Hajj, Shujun Liu, Daniel Sosniak, Peng Zhao, Sulayman D. Dib-Hajj, Stephen G. Waxman
Summary: Neuronal excitability relies on the coordinated action of functionally distinct channels, specifically voltage-gated sodium (Na-v) and potassium (K-v) channels. Mutations and dysfunction of these channels contribute to disorders of excitability, such as pain and epilepsy. Understanding the trafficking of these channels and other axonal proteins can offer potential therapeutic strategies for these diseases. This study demonstrates that various Na-v and K-v channel isoforms and other axonal membrane proteins are co-transported in specific vesicles, providing new insights into the development and organization of sensory neuron membranes.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Cell Biology
Katharina Held, Balazs Istvan Toth
Summary: Ion channels play a crucial role in regulating neural processes in the brain, and disruptions in their functions can lead to various neurological disorders. TRP ion channels are key players in the development and physiological functions of the central nervous system, influencing processes like neurite growth and synaptic plasticity. TRPM3, a non-selective cation channel, is emerging as a new player in the brain with potential roles in neuropathological processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nicholas C. Vierra, James S. Trimmer
Summary: Ion channels in excitable cells play a concerted function in shaping signaling events by controlling membrane electrical properties. Specific groups of ion channels have been recognized to be functionally coupled in mediating ionic fluxes that impact membrane potential, and changes in membrane potential also impact ion channel gating. Recent studies have identified distinct sets of ion channels that can physically and functionally associate to regulate the function of one another. This review discusses canonical and non-canonical ion channel partnerships and their impact.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Clemens L. Schoepf, Cornelia Ablinger, Stefanie M. Geisler, Ruslan Stanika, Marta Campiglio, Walter A. Kaufmann, Benedikt Nimmervoll, Bettina Schlick, Johannes Brockhaus, Markus Missler, Ryuichi Shigemoto, Gerald J. Obermair
Summary: The alpha(2)delta subunits in nerve cells play a critical role in the formation and organization of glutamatergic synapses, with defects leading to synaptic dysfunction and potentially neurological diseases. Each individual alpha(2)delta isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins, suggesting a highly redundant role as synaptic organizers. These findings suggest a shift in understanding of excitatory synapse formation, highlighting the importance of presynaptic differentiation and the potential of alpha(2)delta subunits as nucleation points for synaptic organization.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Xiao Min, Xiaohan Zhang, Shujie Wang, Kyeong-Man Kim
Summary: This study aimed to investigate the activation mechanism of PKC beta II, focusing on the signaling cascade that regulates its phosphorylation and ubiquitination. The researchers found that G beta gamma and 14-3-3 epsilon mediate the constitutive phosphorylation of PKC beta II, which is necessary for its activation. They also discovered that inducible phosphorylation and Mdm2-mediated ubiquitination are required for PKC beta II's translocation to the plasma membrane. These findings will provide insights into the pathogenesis of PKC beta II-related disorders and contribute to their treatment.
Article
Anesthesiology
Huiming Li, Mengjuan Shang, Ling Liu, Xiaoyu Lin, Junfeng Hu, Qian Han, Junling Xing
Summary: Study using a CTT model in mice showed that norepinephrine increases the excitability of small-diameter DRG neurons, which can be attenuated by guanethidine. Abnormal sprouting of nerve fibers in DRG and increased excitability to norepinephrine were observed in CTT mice, making it a useful model to study SMP. Inhibiting the cGMP-PKG pathway attenuated sympathetic sensitivity in CTT mice, suggesting potential for drugs targeting this pathway in treating SMP.
REGIONAL ANESTHESIA AND PAIN MEDICINE
(2021)
Article
Physiology
Jamil Danaf, Carolina da Silveira Scarpellini, Gaspard Montandon
Summary: Opioid medications used for pain management have side-effects like respiratory depression, but the roles of G-protein-coupled receptors and regulator of G-protein signaling in this process are not fully understood. Pharmacological modulation of these factors showed that G-proteins play a significant role in reversing respiratory depression, while RGS4 does not affect this process. These findings suggest that targeting G-proteins could be a potential strategy for developing opioid overdose antidotes.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biology
Pradeep Bhandari, David Vandael, Diego Fernandez-Fernandez, Thorsten Fritzius, David Kleindienst, Cihan Onal, Jacqueline Montanaro, Martin Gassmann, Peter Jonas, Akos Kulik, Bernhard Bettler, Ryuichi Shigemoto, Peter Koppensteiner
Summary: The study found that KCTD8 and KCTD12b directly bind to Cav2.3 and co-localize in the rostral IPN. These KCTDs modulate synaptic strength by regulating Cav2.3-mediated release, independent of GBR activation.
Article
Biochemistry & Molecular Biology
Uma Anand, Praveen Anand, Mikael Hans Sodergren
Summary: Terpenes in Cannabis sativa inhibit capsaicin-induced calcium influx by activating Na+/K+ ATPase, which contributes to their analgesic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Vivian Gonzalez-Perez, Yu Zhou, Matthew A. Ciorba, Christopher J. Lingle
Summary: Large conductance K+ channels (BK channels), regulated by cell-specific subunits, play important roles in various cellular and physiological functions. LRRC26, a member of the LRRC family, not only functions as a tumor suppressor, but is also highly expressed in secretory epithelial cells and regulates BK channels to maintain normal secretory function. LRRC26 may also be important in other organs like airways, female reproductive tract, and mammary gland. Future research should focus on understanding the mechanisms of LRRC-dependent pathologies and their impact on gene regulation.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Daisy J. Grove, Daniel J. Levine, Michael G. Kearse
Summary: Researchers developed a new purification method to obtain large amounts of soluble recombinant human eIF2A protein. Their experiments revealed that excess eIF2A inhibits translation of multiple mRNAs, including those with cognate and near-cognate start codons, and does so before start codon recognition. eIF2A also inhibits translation directed by all four types of cap-independent viral IRESs, suggesting it sequesters 40S subunits. These findings uncover the mechanism by which eIF2A regulates translation through binding with 40S ribosomal subunits.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Natsumi Maruta, Yuri Trusov, Alan M. Jones, Jose R. Botella
Summary: Plant G proteins consist of canonical G alpha subunits and unconventional XLG subunits, interacting with G beta gamma dimers and RGS protein, and participating in development, stress responses, and immunity. Despite the overall similarity between plant and animal G alpha subunits, they convey signals differently.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jong-Chan Park, Alex Luebbers, Maria Dao, Ana Semeano, Anh Minh Nguyen, Maria P. Papakonstantinou, Stefan Broselid, Hideaki Yano, Kirill A. Martemyanov, Mikel Garcia-Marcos
Summary: In this study, researchers uncover a new mechanism of G protein regulation involving the protein GINIP, which biases inhibitory GPCR responses towards Gbg signaling and dampens Gai-GTP signaling. This mechanism is crucial for maintaining balanced neurotransmission and preventing increased seizure susceptibility in mice.
Article
Multidisciplinary Sciences
Andres Hernandez-Clavijo, Cesar Adolfo Sanchez Trivino, Giorgia Guarneri, Chiara Ricci, Fabian A. Mantilla-Esparza, Kevin Y. Gonzalez-Velandia, Paolo Boscolo-Rizzo, Margherita Tofanelli, Pierluigi Bonini, Michele Dibattista, Giancarlo Tirelli, Anna Menini
Summary: The COVID-19 pandemic highlighted our limited understanding of human olfactory physiology. By using acute slices of human olfactory epithelium and whole-cell patch-clamp technique, this study characterized the electrical properties of olfactory sensory neurons and supporting cells. The study also demonstrated the intact transduction cascade in this preparation through responses to odorant mixtures. This research provides valuable insights into human olfactory physiology and lays the foundation for future studies.
Review
Biochemistry & Molecular Biology
Jan H. Voss, Christa E. Muller
Summary: G protein-coupled receptors are the most important class of drug targets in the human body, transmitting extracellular signals into the cytosol through interaction with Gα proteins. Direct inhibition of Ga protein subunits has been proposed as a novel strategy for treating complex diseases.
CURRENT MEDICINAL CHEMISTRY
(2022)