Article
Agriculture, Multidisciplinary
Lianyun Lin, Heng Jiang, Hadiatullah Hadiatullah, Ruifang Ma, Henryk Korza, Yucheng Gu, Zhiguang Yuchi
Summary: The study reveals that insect calmodulin (CaM) regulates the RyR receptor in agricultural pests, and the enhanced binding of CaM in mutant insect RyR leads to increased sensitivity to insecticides, suggesting the potential targeting of the CaM-CaMBD interface by molecular glues.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Cell Biology
Matteo Serano, Laura Pietrangelo, Cecilia Paolini, Flavia A. Guarnier, Feliciano Protasi
Summary: Calsequestrin 1 (CASQ1) and Ryanodine receptor 1 (RYR1) play important roles in excitation-contraction coupling. CASQ1-null and Y522S mice have increased food consumption, higher core temperature at rest, and increased oxygen consumption. Y522S mice are more susceptible to hypermetabolic crises compared to CASQ1-null mice.
Article
Cardiac & Cardiovascular Systems
Dmytro O. Kryshtal, Daniel J. Blackwell, Christian L. Egly, Abigail N. Smith, Suzanne M. Batiste, Jeffrey N. Johnston, Derek R. Laver, Bjorn C. Knollmann
Summary: The main mechanism of antiarrhythmic action of flecainide is likely through inhibition of RyR2-mediated arrhythmogenic Ca release, rather than solely through sodium channel block. Experimental results in cardiomyocytes and mouse models have both confirmed this.
CIRCULATION RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Review
Cell Biology
John A. P. Rostas, Kathryn A. Skelding
Summary: This review summarizes the structure and regulation of CaMKII, and explores how the molecular environment and interaction with binding partner proteins can lead to different populations of CaMKII in various cells or subcellular locations, resulting in diverse functional responses to activation by increased intracellular calcium concentration. It also proposes that identifying the molecular interactions responsible for the targeting of CaMKII in specific cells and determining the sites of interaction could lead to the development of highly selective inhibitors for specific CaMKII-mediated functional responses, with potential therapeutic implications.
Article
Biochemistry & Molecular Biology
Angelos Thanassoulas, Maria Theodoridou, Laila Barrak, Emna Riguene, Tamader Alyaarabi, Mohamed A. Elrayess, F. Anthony Lai, Michail Nomikos
Summary: This study investigates the role of Calmodulin (CaM) in regulating the cardiac ryanodine receptor 2 (RyR2) and its potential contribution to cardiac arrhythmia. It reveals that two specific regions of RyR2 bind with high affinity to CaM and that a missense CaM mutation (E105A) dysregulates normal cardiac function. The study also shows that the E105A mutation negatively affects the interaction between CaM and the RyR2 regions, highlighting their importance in channel regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Fujian Lu, Qing Ma, Wenjun Xie, Carter L. Liou, Donghui Zhang, Mason E. Sweat, Blake D. Jardin, Francisco J. Naya, Yuxuan Guo, Heping Cheng, William T. Pu
Summary: This study uncovers the role of CMYA5 in organizing and regulating the subcellular structures in cardiomyocytes, highlighting its importance in cardiac development, function, and tolerance to pressure overload.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Lulu Jiang, Pijush Chakraborty, Lushuang Zhang, Melissa Wong, Shannon E. Hill, Chelsea Joy Webber, Jenna Libera, Laura J. Blair, Benjamin Wolozin, Markus Zweckstetter
Summary: Alzheimer's disease and related tauopathies are characterized by misfolding and aggregation of the protein tau. This study demonstrates that the immunophilin FKBP12 regulates neuronal resilience by acting as a chaperone for monomeric tau. The study identifies the molecular factors involved in FKBP12's binding to tau and its influence on tau-induced neurotoxicity.
Article
Cardiac & Cardiovascular Systems
Cathrine R. Carlson, Jan Magnus Aronsen, Anna Bergan-Dahl, Marie Christine Moutty, Marianne Lunde, Per Kristian Lunde, Hilde Jarstadmarken, Pimthanya Wanichawan, Laetitia Pereira, Terje R. S. Kolstad, Bjorn Dalhus, Hariharan Subramanian, Susanne Hille, Geir Christensen, Oliver J. Mueller, Viacheslav Nikolaev, Donald M. Bers, Ivar Sjaastad, Xin Shen, William E. Louch, Enno Klussmann, Ole M. Sejersted
Summary: This study demonstrates that AKAP18 delta anchors and regulates CaMKII activity at the sarcoplasmic reticulum, contributing to the regulation of cardiac contraction and relaxation.
CIRCULATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Carlo Manno, Eshwar Tammineni, Lourdes Figueroa, Isabelle Marty, Eduardo Rios
Summary: Triadin plays a key role in regulating calcium signaling and muscle function. Its knockout leads to alterations in calcium balance and changes in the expression of important proteins, such as calsequestrin. However, the muscle cells are able to compensate for these changes and maintain normal muscle function.
Article
Biochemistry & Molecular Biology
Angelos Thanassoulas, Vyronia Vassilakopoulou, Brian L. Calver, Luke Buntwal, Adrian Smith, Christopher Lai, Iris Kontogianni, Evangelia Livaniou, George Nounesis, F. Anthony Lai, Michail Nomikos
Summary: In this study, four missense CaM mutants were generated and their interactions with RyR2 were compared to wild-type CaM using co-immunoprecipitation and [H-3]ryanodine binding assays. The functional effects of these CaM mutations on RyR2 activity were also investigated. The results showed that all four CaM mutants displayed reduced RyR2 interaction and defective modulation of [H-3]ryanodine binding to RyR2, regardless of LQTS or CPVT association.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Biochemistry & Molecular Biology
Brianna D. Young, Kristen M. Varney, Paul T. Wilder, Brianna K. Costabile, Edwin Pozharski, Mary E. Cook, Raquel Godoy-Ruiz, Oliver B. Clarke, Filippo Mancia, David J. Weber
Summary: The interaction between calmodulin (CaM) and the retinol uptake receptor STRA6 involves binding of a peptide derived from BP2 to the C-lobe of CaM in low free Ca2+ concentrations. As free Ca2+ levels increase, BP2 also interacts with the N-lobe of CaM. This structural rearrangement could be relevant to vitamin A transport by the full-length (CaM)-Ca-Ca-STRA6 complex as intracellular Ca2+ concentrations approach those typical of a Ca2+-signaling event.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Konstantin E. Komolov, Sarah M. Sulon, Anshul Bhardwaj, Sin C. van Keulen, Nguyen Minh Duc, Daniela K. Laurinavichyute, Hua Jane Lou, Benjamin E. Turk, Ka Young Chung, Ron O. Dror, Jeffrey L. Benovic
Summary: In this study, the complex of CaM with GRK5 was analyzed structurally, computationally, and biochemically to reveal how CaM modulates GRK5 response to calcium, leading to activation and localization effects for selective substrate targeting by GRK5.
Article
Cell & Tissue Engineering
Daniel J. Clemens, Dan Ye, Lili Wang, C. S. John Kim, Wei Zhou, Steven M. Dotzler, David J. Tester, Isabelle Marty, Bjorn C. Knollmann, Michael J. Ackerman
Summary: TKOS is a malignant arrhythmia disorder caused by recessive null variants in TRDN-encoded cardiac triadin. iPSC-CMs generated from TKOS patients and a control were used to study the effects of triadin knockout. The loss of triadin resulted in prolonged action potential duration and disrupted calcium handling proteins, leading to frequent cellular arrhythmias in TKOS model cells.
Article
Biochemistry & Molecular Biology
Tomoyuki Uchida, Tetsuro Oda, Takeshi Yamamoto, Masako Inamitsu, Chihiro Sakai, Hitoshi Uchinoumi, Takeshi Suetomi, Yoshihide Nakamura, Yoko Okamoto, Satomi Tateda, Shohei Fujii, Shinji Tanaka, Junya Nawata, Takayuki Okamura, Shigeki Kobayashi, Masafumi Yano
Summary: The study reveals that endoplasmic reticulum stress causes the translocation of calmodulin to the nucleus and drives the phenotypic switching of vascular smooth muscle cells. Restoring the binding affinity of calmodulin to ryanodine receptor may be a potential therapeutic target for atherosclerosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)