Article
Multidisciplinary Sciences
Xiumin Chen, Yuko Fukata, Masaki Fukata, Roger A. Nicoll
Summary: This study reveals the essential role of the MAGUK family of synaptic scaffolding proteins in LTP, with PSD-95 requiring binding to ADAM22 for synaptic transmission enhancement. Additionally, an alternative pathway involving SAP102 is proposed, independent of ADAM22.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Chao-Hua Jiang, Mengping Wei, Chen Zhang, Yun Stone Shi
Summary: Long-term potentiation (LTP) is a crucial cellular mechanism for learning and memory, with the amino-terminal domain (ATD) of GluA1 interacting with neuroplastin-65 (Np65) playing a key role in anchoring AMPARs at the postsynaptic membrane during LTP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Ian D. Coombs, Stuart G. Cull-Candy
Summary: The functional properties of AMPA receptors are crucial in shaping excitatory synaptic signaling in the brain. Understanding the behavior and regulation of single AMPAR channels is essential in unraveling how central synapses carry, process, and store information. Auxiliary subunits play a key role in regulating AMPAR channel properties and adding diversity, while single-channel studies reveal the unique behavior of AMPAR channels.
Article
Multidisciplinary Sciences
Shuo Li, Sumana Raychaudhuri, Stephen Alexander Lee, Marisa M. Brockmann, Jing Wang, Grant Kusick, Christine Prater, Sarah Syed, Hanieh Falahati, Raul Ramos, Tomas M. Bartol, Eric Hosy, Shigeki Watanabe
Summary: Neurotransmitter release in synapses is influenced by action potentials, with synchronous and asynchronous release sites segregated within active zones, aligned with AMPA and NMDA receptor clusters respectively. This organization leads to efficient activation of NMDA receptors, enhancing membrane depolarization through AMPA receptors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Matthew McCallum, Anna De Marco, Florian Lempp, M. Alejandra Tortorici, Dora Pinto, Alexandra C. Walls, Martina Beltramello, Alex Chen, Zhuoming Liu, Fabrizia Zatta, Samantha Zepeda, Julia di Iulio, John E. Bowen, Martin Montiel-Ruiz, Jiayi Zhou, Laura E. Rosen, Siro Bianchi, Barbara Guarino, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Paul W. Rothlauf, Louis-Marie Bloyet, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Agostino Riva, Gyorgy Snell, Amalio Telenti, Sean P. J. Whelan, Herbert W. Virgin, Davide Corti, Matteo Samuele Pizzuto, David Veesler
Summary: The study identifies 41 human monoclonal antibodies that recognize the N-terminal domain of the SARS-CoV-2 spike protein and exhibit strong neutralizing activity. These antibodies inhibit cell-to-cell fusion, activate effector functions, and protect animals from virus challenge, highlighting the importance of NTD-specific neutralizing antibodies for protective immunity and vaccine development. Several SARS-CoV-2 variants with mutations in the NTD supersite suggest ongoing selective pressure on the virus.
Article
Pharmacology & Pharmacy
Katarzyna Terejko, Michal A. Michalowski, Anna Dominik, Anna Andrzejczak, Jerzy W. Mozrzymas
Summary: Recent studies have shown that the activation of pLGICs is associated with coordinated subunit twisting in the membrane plane, indicating a crucial role of intersubunit interactions in receptor activation, especially in preactivation and opening processes. The underlying mechanisms of this intersubunit cross-talk outside the top-down pathway remain largely unknown.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Carol A. Harley, Ganeko Bernardo-Seisdedos, Whitney A. Stevens-Sostre, David K. Jones, Maria M. Azevedo, Paula Sampaio, Marta Lorga-Gomes, Matthew C. Trudeau, Oscar Millet, Gail A. Robertson, Joao H. Morais-Cabral
Summary: Research has shown that single-chain variable fragment antibodies can modulate hERG channel function by binding to the PAS domain and generate a Förster resonance energy transfer signal in the channel open state. The state dependence of the FRET signal disappears when a mutation that disrupts the PAS-CNBh interaction is introduced.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Kristine F. R. Pobre-Piza, Melissa J. Mann, Ashley R. Flory, Linda M. Hendershot
Summary: The co-chaperones BiP, ERdj4, ERdj5, and GRP170 associate with aggregation-prone peptides. In this study, the impact of Interstitial Lung Disease (ILD)-associated mutants of surfactant protein C (SP-C) on protein maturation is investigated. The authors demonstrate that the ILD mutants disrupt di-sulfide bond formation and expose aggregation-prone peptides, leading to binding with ERdj4, ERdj5, and GRP170. Furthermore, the destabilized mutant BRICHOS domain affects the insertion of its transmembrane (TM) region in the ER membrane. This study provides insights into chaperone specificity, the recognition of aggregation-prone regions, and the consequences of disease-associated mutants on protein folding.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Amanda M. Perozzo, Jochen Schwenk, Aichurok Kamalova, Terunaga Nakagawa, Bernd Fakler, Derek Bowie
Summary: This study reveals the unique characteristics of GSG1L in terms of its spatiotemporal expression, composition, and functionality. It is expressed late during brain development in a region-specific manner and constitutes about 5% of all AMPAR complexes in adulthood. GSG1L can assemble with TARPs or CNIHs, but it also has the ability to function as the sole auxiliary subunit. Through its interaction with two evolutionarily conserved sites on the agonist-binding domain, GSG1L weakly slows desensitization at the TARP/KGK site and strongly slows recovery from desensitization at a different site. These findings provide insights into the unique signaling role of GSG1L within glutamatergic synapses.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mohammad Qneibi, Nidal Jaradat, Nawaf Al-Maharik, Mohammed Hawash, Linda Issa, Shorooq Suboh, Leen Yahya, Adan Abu Khait, Amjaad Warasneh, Sosana Bdir
Summary: The study investigates the composition and effects of Lavandula coronopifolia essential oil (EO) on cancer cells and AMPA receptor subunits. The EO shows high contents of eucalyptol, beta-pinene, and alpha-pinene. It demonstrates significant antiproliferative selectivity against HepG2 cancer cell lines and affects AMPA receptor kinetics. These findings suggest potential therapeutic use of Lavandula coronopifolia EO in cancer treatment and neurodegenerative diseases.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Masayuki Iwamoto, Masayuki Morito, Shigetoshi Oiki, Yudai Nishitani, Daisuke Yamamoto, Nobuaki Matsumori
Summary: The study reveals that dianionic cardiolipin (CL) has higher affinity for KcsA and can bind to both the N-terminal M0 helix and a specific site, while monoanionic lipids primarily interact with the M0 helix. This suggests the presence of an alternative CL-binding site in the transmembrane domain. Furthermore, CL enhances the channel opening independently of the M0 helix, while the action of monoanionic lipids is mediated solely by the M0 helix.
Article
Biochemistry & Molecular Biology
Roa'a Jaradat, Xiaole Li, Honghong Chen, Peter B. Stathopulos, Donglin Bai
Summary: Functional studies and structural models of Cx46 and Cx50 GJs reveal the importance of hydrophobic interactions between the NT and TM2 domains in V-j-gating, gamma(j), and channel open stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xuan Ling Hilary Yong, Lingrui Zhang, Liming Yang, Xiumin Chen, Jing Zhi Anson Tan, Xiaojun Yu, Mintu Chandra, Emma Livingstone, Jocelyn Widagdo, Marta M. Vieira, Katherine W. Roche, Joseph W. Lynch, Angelo Keramidas, Brett M. Collins, Victor Anggono
Summary: The study reveals that phosphorylation of GluN2A at Ser-1459 by CaMKII alpha in response to glycine stimulation enhances the endosomal recycling of NMDARs through interaction with SNX27-retromer complex. Mutations of Ser-1459 prolong the decay times of NMDAR-mediated synaptic currents, including the S1459G variant associated with epilepsy, by increasing channel opening duration. These findings highlight the critical role of Ser-1459 phosphorylation in regulating NMDAR function.
Article
Biology
Jiangchao Xiang, Jie Su, Qiaoshuai Lan, Wenwen Zhao, Yu Zhou, Youwei Xu, Jun Niu, Shuai Xia, Qilian Qi, Sachdev Sidhu, Lu Lu, Shane Miersch, Bei Yang
Summary: Understanding the antigenic signatures of human coronaviruses is crucial for vaccine development. Researchers have identified antigenic sites in the S proteins of HCoV-229E and HCoV-NL63, which may serve as targets for pan-alpha-HCoVs vaccines. They have also discovered a neutralizing antibody that targets the connector domain, representing the first S2-directed neutralizing antibody against alpha-HCoVs. These findings provide insights into the antigenic landscape of alpha-HCoVs S proteins and the challenges and opportunities in pan-HCoV vaccine design.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Ashley M. Bourke, Samantha L. Schwartz, Aaron B. Bowen, Mason S. Kleinjan, Christina S. Winborn, Dean J. Kareemo, Amos Gutnick, Thomas L. Schwarz, Matthew J. Kennedy
Summary: The study introduces a new method, zapERtrap, which enables precise triggering of forward trafficking of integral membrane proteins from internal secretory organelles to the cell surface using light. By applying this method in neurons, the researchers revealed the locations where synaptic proteins emerge at the cell surface through central or remote secretory pathways, providing new insights into compartmentalized secretory trafficking.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Neurosciences
James Krieger, Ji Young Lee, Ingo H. Greger, Ivet Bahar
NEUROSCIENCE LETTERS
(2019)
Review
Biochemistry & Molecular Biology
Olivia R. Buonarati, Erik A. Hammes, Jake F. Watson, Ingo H. Greger, Johannes W. Hell
Article
Biochemistry & Molecular Biology
Ji Young Lee, James Krieger, Beatriz Herguedas, Javier Garcia-Nafria, Anindita Dutta, Saher A. Shaikh, Ingo H. Greger, Ivet Bahar
Article
Multidisciplinary Sciences
Beatriz Herguedas, Jake F. Watson, Hinze Ho, Ondrej Cais, Javier Garcia-Nafria, Ingo H. Greger
Article
Multidisciplinary Sciences
Ian D. Coombs, David Soto, Thomas P. McGee, Matthew G. Gold, Mark Farrant, Stuart G. Cull-Candy
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Jan-Niklas Dohrke, Jake F. Watson, Kristian Birchall, Ingo H. Greger
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemical Research Methods
Hinze Ho, Adam Fowle, Marisa Coetzee, Ingo H. Greger, Jake F. Watson
JOURNAL OF NEUROSCIENCE METHODS
(2020)
Review
Neurosciences
Stuart G. Cull-Candy, Mark Farrant
Summary: CP-AMPARs are important regulators of synaptic plasticity, with their functional characteristics being modulated by auxiliary subunits and involved in various forms of central synaptic plasticity. Maladaptive synaptic plasticity and neurological disorders often involve changes in CP-AMPAR expression, such as those induced by inflammatory pain, fear conditioning, and cocaine exposure.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Danyang Zhang, Jake F. Watson, Peter M. Matthews, Ondrej Cais, Ingo H. Greger
Summary: This study reveals the structure and active states of AMPAR complexes, demonstrating that TARP-gamma 8 and CNIH2 affect the gating regulation of AMPARs by binding to specific regions of the receptor, thereby promoting the transition to the active-state conformation.
Article
Multidisciplinary Sciences
Beatriz Herguedas, Bianka K. Kohegyi, Jan-Niklas Dohrke, Jake F. Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, Ingo H. Greger
Summary: This study reveals how the auxiliary subunit TARP-gamma 8 modulates the gating kinetics, ion conductance, and rectification properties of AMPA receptors, providing important insights into the functional mechanism of AMPA glutamate receptors.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Ian D. Coombs, Craig A. Sexton, Stuart G. Cull-Candy, Mark Farrant
Summary: AMP-type glutamate receptors play a crucial role in excitatory signaling in the brain and have therapeutic potential for neurological disorders. Research on selective inhibitors targeting the auxiliary subunit TARP y8 provides insights into the mechanism of action and potential treatment strategies.
MOLECULAR PHARMACOLOGY
(2022)
Article
Clinical Neurology
Ian D. Coombs, Julie Ziobro, Volodymyr Krotov, Taryn-Leigh Surtees, Stuart G. Cull-Candy, Mark Farrant
Summary: In this study, a novel gain-of-function mutation in the GRIA2 gene was identified, leading to enhanced GluA2 A643V receptor activity. The results suggest that perampanel may have therapeutic efficacy for GRIA2 mutation-related disorders.
Article
Biology
Ian Coombs, Cecile Bats, Craig A. Sexton, Dorota Studniarczyk, Stuart G. Cull-Candy, Mark Farrant
Summary: Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) play important roles in synaptic plasticity and pathology. The presence of auxiliary subunits complicates the interpretation of current rectification as a measure of CP-AMPAR expression. However, the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution can block GluA1-mediated outward currents regardless of the auxiliary subunit type, providing a functional measure of CP-AMPARs.