Article
Cell Biology
James H. Baraniak, Yandong Zhou, Robert M. Nwokonko, Michelle R. Jennette, Sarah A. Kazzaz, Jazmin M. Stenson, Abigale L. Whitsell, Youjun Wang, Mohamed Trebak, Donald L. Gill
Summary: The study reveals that the interaction between M4x peptides in Orai channels and STIM1 protein can block Ca2+ signal transduction and affect the coupling between STIM and Orai proteins, thereby regulating the cell's Ca2+ signaling pathway.
Article
Genetics & Heredity
Selvan Bavan, Howard P. Goodkin, Diane M. Papazian
Summary: Kv4.2 subunits, encoded by KCND2, are pore-forming components of voltage-gated, inactivating I-SA K+ channels expressed in the brain. Two de novo variants in Kv4.2, p.Val404Met and p.Val402Leu, are associated with infant-onset developmental and epileptic encephalopathy and early-onset pharmacoresistant epilepsy, respectively. Both variants enhance inactivation from closed states, but impair inactivation after channel opening.
Article
Biology
Cheon-Gyu Park, Wookyung Yu, Byung-Chang Suh
Summary: This study found that Ca-v beta subunits regulate the biophysical states of Ca-v 2.2 channels by modulating the interaction with different PIP2 binding sites.
Article
Multidisciplinary Sciences
Ana I. Fernandez-Marino, Xiao-Feng Tan, Chanhyung Bae, Kate Huffer, Jiansen Jiang, Kenton J. Swartz
Summary: The study reveals the structure and functional mechanisms of the Kv2.1 voltage-activated potassium channel, providing insights into how mutations affect channel activity. Inactivation in Kv2.1 is found to be caused by dynamic alterations in electromechanical coupling, which suggests a conserved mechanism in voltage-activated cation channels and its relevance for regulating neuron firing.
Article
Medicine, Research & Experimental
Alexandra A. Bouza, Nnamdi Edokobi, Samantha L. Hodges, Alexa M. Pinsky, James Offord, Lin Piao, Yan-Ting Zhao, Anatoli N. Lopatin, Luis F. Lopez-Santiago, Lori L. Isom
Summary: Loss-of-function variants in SCN1B, which encode voltage-gated sodium channel beta 1 subunits, are associated with high-risk human diseases including developmental and epileptic encephalopathy and cardiac arrhythmia. The modulation of sodium channel pore-forming ix subunits by beta 1 subunits, which are involved in various cellular processes, suggests a complex role for beta 1 in cellular function. Investigating the regulated intramembrane proteolysis (RIP) of beta 1 by BACE1 and gamma-secretase provides insights into how SCIV1B LOF variants may lead to transcriptional dysregulation and altered excitability.
Article
Multidisciplinary Sciences
Adam Feher, Zoltan Petho, Tibor G. Szanto, Almos Klekner, Gabor Tajti, Gyula Batta, Tibor Hortobagyi, Zoltan Varga, Albrecht Schwab, Gyorgy Panyi
Summary: This study found functional expression of K(Ca)1.1/β3 complex in glioblastoma cells, suggesting its potential diagnostic and therapeutic role in glioblastoma.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Rawad Hodeify, Maya Dib, Ethel Alcantara-Adap, Raphael Courjaret, Nancy Nader, Cleo Z. Reyes, Ayat S. Hammad, Satanay Hubrack, Fang Yu, Khaled Machaca
Summary: This study elucidates the regulation of Orai1 endocytosis during meiosis by the C-terminal structure, specifically through a region called the C-terminus Internalization Handle (CIH). The strength of intersubunit coiled coil (CC) domains controls access to CIH and ultimately affects Orai1 internalization. The findings suggest that Orai1 endocytosis requires both the N-terminal caveolin binding motif (CBM) and the C-terminal CIH, with access to CIH being influenced by the strength of intersubunit C-terminal CC.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Flavio Costa, Carlo Guardiani, Alberto Giacomello
Summary: This study investigated the activation/deactivation mechanism of hERG, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including Long QT Syndrome. The results revealed two distinct pathways connecting the voltage sensor domain with the pore domain, and identified LQTS-related mutations distributed along these pathways, providing a microscopic interpretation of their role. Additionally, it was found that the channel still functions as a gate even when a cut is introduced between the voltage sensor domain and the neighboring helix S5.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Carlos A. Z. Bassetto, Flavio Costa, Carlo Guardiani, Francisco Bezanilla, Alberto Giacomello
Summary: This article reveals the existence of a noncanonical kinematic chain of residues involving the S4/S1 and S1/S5 subunit interfaces that controls the gating of the hERG cardiac channel, which is vital for the function of organs such as the brain, heart, and muscles.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Guohui Zhang, Xianjin Xu, Zhiguang Jia, Yanyan Geng, Hongwu Liang, Jingyi Shi, Martina Marras, Carlota Abella, Karl L. Magleby, Jonathan R. Silva, Jianhan Chen, Xiaoqin Zou, Jianmin Cui
Summary: Researchers have discovered a compound, BC5, that interacts with the CTD-VSD interface and specifically modulates the Ca2+ dependent activation mechanism. BC5 can activate the channel in the absence of Ca2+ binding, but Ca2+ binding inhibits BC5 effects. This study reveals the importance of the CTD-VSD interaction in the Ca2+ activation mechanism and provides insights for allosteric agonists to modulate BK channel activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hartwig Seitter, Jana Obkircher, Patricia Grabher, Julia Hartl, Lucia Zanetti, Uwe Thorsten Lux, Georgios Fotakis, Monica L. Fernandez-Quintero, Teresa Kaserer, Alexandra Koschak
Summary: This study discovered and characterized a novel Cav[12 variant in the retina, which contains a unique N-terminus with a high concentration of hydrophobic residues. This variant has distinct biophysical properties and exhibits strong membrane association and clustering. Further investigation of this variant could provide new insights into the molecular mechanisms of how Cav[1 subunits modulate Ca2+ channels at the plasma membrane.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Physiology
Guanxing Chen, Qin Li, Timothy I. Webb, Mark A. Hollywood, Jiusheng Yan
Summary: This study identifies positively charged peptides as modulators of BK channels, and reveals a role for the Ca2+-bowl site and the C-terminal positively charged regions of auxiliary gamma subunits in BK channel modulation. The positively charged peptides and the cationic HIV-1 Tat peptide can shift the voltage-gating of BK channels towards hyperpolarization. The modulatory effects of the synthetic peptides are reduced in the presence of Ca2+ and can be abolished by charge neutralization of the Ca2+-bowl site and high ionic strength.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ryan Mahling, Cade R. Rahlf, Samuel C. Hansen, Matthew R. Hayden, Madeline A. Shea
Summary: FGFs and CaM directly bind to the Na-V channel and play a key role in regulating channel function, especially A-type FGFs can compete with (Ca2+)(4)-CaM for binding, thereby modulating channel function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dilip Rai, Takumi Akagi, Atsushi Shimohata, Toshiyuki Ishii, Mie Gangi, Takuma Maruyama, Yuko Wada-Kiyama, Ikuo Ogiwara, Makoto Kaneda
Summary: The intracellular C-terminal domain of mGluR6 is essential for its cell surface localization and receptor function, with specific amino acid deletions affecting these processes. The CTD may also contain regulatory elements for intracellular trafficking and signaling, as indicated by conservation of amino acids resembling an ER retention motif.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Physiology
Jacob M. Kemp, Dominic G. Whittaker, Ravichandra Venkateshappa, ZhaoKai Pang, Raj Johal, Valentine Sergeev, Glen F. Tibbits, Gary R. Mirams, Thomas W. Claydon
Summary: The study demonstrates that the hERG channel activator RPR260243 enhances repolarizing currents during the refractory period, particularly in LQTS2 and arrhythmia cases. This provides a targeted antiarrhythmic potential without the risk of early repolarization in certain hERG variants.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Biophysics
Jessica Wollberg, Robert Baehring
BIOPHYSICAL JOURNAL
(2016)
Article
Oncology
Sergey A. Dyshlovoy, Katharina Otte, Winfried H. Alsdorf, Jessica Hauschild, Tobias Lange, Simone Venz, Christiane K. Bauer, Robert Baehring, Kerstin Amann, Ramin Mandanchi, Udo Schumacher, Jennifer Schroeder-Schwarz, Tatyana N. Makarieva, Alla G. Guzii, Kseniya M. Tabakmakher, Sergey N. Fedorov, Larisa K. Shubina, Igor E. Kasheverov, Heimo Ehmke, Thomas Steuber, Valentin A. Stonik, Carsten Bokemeyer, Friedemann Honecker, Gunhild von Amsberg
Article
Physiology
Christiane Groen, Robert Baehring
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2017)
Article
Multidisciplinary Sciences
Lara Waldschmidt, Vera Junkereit, Robert Baehring
Article
Multidisciplinary Sciences
Helena Prechtel, Sven Hartmann, Daniel Mingecurrency, Robert Baehring
Article
Education, Scientific Disciplines
Robert Baehring, Christiane K. Bauer
ADVANCES IN PHYSIOLOGY EDUCATION
(2014)
Article
Cell Biology
Sabine Windhorst, Daniel Minge, Robert Baehring, Svenja Hueser, Claudia Schob, Christine Blechner, Hong-Ying Lin, Georg W. Mayr, Stefan Kindler
CELLULAR SIGNALLING
(2012)
Review
Biochemistry & Molecular Biology
Robert Baehring
Article
Biochemistry & Molecular Biology
Wiebke Wilkars, Jessica Wollberg, Evita Mohr, Mieri Han, Dane M. Chetkovich, Robert Baehring, Roland A. Bender
Review
Neurosciences
Robert Baehring, Manuel Covarrubias
JOURNAL OF PHYSIOLOGY-LONDON
(2011)
Article
Neurosciences
Frank F. Heisler, Sven Loebrich, Yvonne Pechmann, Nikolaus Maier, Aleksandar R. Zivkovic, Mariko Tokito, Torben J. Hausrat, Michaela Schweizer, Robert Baehring, Erika L. F. Holzbaur, Dietmar Schmitz, Matthias Kneussel
Article
Neurosciences
Katrin Witzel, Paul Fischer, Robert Baehring
Review
Pharmacology & Pharmacy
Robert Baehring, Jan Barghaan, Regina Westermeier, Jessica Wollberg
FRONTIERS IN PHARMACOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Carolin Seifert, Stephan Storch, Robert Baehring
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Yongqiang Zhang, Georgios Tachtsidis, Claudia Schob, Mahmoud Koko, Ulrike B. S. Hedrich, Holger Lerche, Johannes R. Lemke, Arie van Haeringen, Claudia Ruivenkamp, Trine Prescott, Kristian Tveten, Thorsten Gerstner, Brianna Pruniski, Stephanie DiTroia, Grace E. VanNoy, Heidi L. Rehm, Heather McLaughlin, Hanno J. Bolz, Ulrich Zechner, Emily Bryant, Tiffani McDonough, Stefan Kindler, Robert Baehring
Summary: This study reports six individuals with early-onset global developmental delay carrying heterozygous missense variants of KCND2, resulting in impaired Kv4.2 channel gating. The results support the role of Kv4.2 channel gating impairment in early-onset monogenic global developmental delay.
HUMAN MOLECULAR GENETICS
(2021)