Article
Biochemistry & Molecular Biology
Veronica A. Cochrane, Zhongying Yang, Mark L. Dell'Acqua, Show-Ling Shyng
Summary: The study revealed that leptin regulates the trafficking of K-ATP channels in pancreatic beta-cells by affecting PKA activity. Increased PKA activity depends on NMDA receptors, CaMKK beta, and AMPK, and is anchored to AKAP79/150 at the cell membrane. disrupting AKAP79/150 coordination may provide a potential target for restoring insulin secretion in beta-cells with defective leptin signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sally Prueschenk, Michael Majer, Rainer Schreiber, Jens Schlossmann
Summary: IRAG2, also known as Jaw1 or LRMP, interacts with IP3 receptors to modulate intracellular Ca2+ signaling and exocrine pancreatic function. Loss of IRAG2 results in decreased basal levels of intracellular Ca2+ and impacts amylase secretion. This suggests that IRAG2 plays a role in regulating exocrine pancreatic function through modulating intracellular Ca2+ signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Lei Li, Haowen Liu, Mia Krout, Janet E. Richmond, Yu Wang, Jihong Bai, Saroja Weeratunga, Brett M. Collins, Donovan Ventimiglia, Yi Yu, Jingyao Xia, Jing Tang, Jie Liu, Zhitao Hu
Summary: This study identifies a dual Ca2+ sensor system in C. elegans, with SNT-1 and SNT-3 triggering neurotransmitter release at different rates. While SNT-1 is tethered to synaptic vesicles, SNT-3 functions independently of vesicles.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Rafiquel Sarker, Ruxian Lin, Varsha Singh, Mark Donowitz, Chung -Ming Tse
Summary: In polarized intestinal epithelial cells, the downregulated in adenoma (DRA) is involved in both NaCl absorption and anion secretion. Forskolin (FSK) and adenosine 50-triphosphate (ATP) can stimulate the activity of DRA in a concentration-dependent manner. The synergistic increase of intracellular Ca2+ is essential for the stimulation of DRA by FSK and ATP.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Cell Biology
Mikayla R. Erdelsky, Sarah A. Groves, Charmi Shah, Samantha B. Delios, M. Bibiana Umana, Donald H. Maurice
Summary: Recent evidence suggests that cAMP signaling within the primary cilium plays a crucial role in promoting adipogenic differentiation of 3T3-L1 preadipocytes. In this study, the researchers identified the specific cAMP phosphodiesterases expressed by these cells and found that inhibition of PDE4 promotes FFAR4-mediated adipogenesis. This work could potentially lead to the discovery of more targeted therapeutic approaches for controlling adipogenesis and differentiation of other stem cells.
CELLULAR SIGNALLING
(2024)
Article
Medicine, Research & Experimental
Xin Deng, Jia Ma, Wenyang Zhou, Yifeng Yuan, Baosheng Wang, Xiangpeng Meng
Summary: Dysregulation of the GID2 protein, an E3 ubiquitin ligase subunit of the GID complex, is associated with pancreatic cancer progression. High GID2 expression in clinical samples is correlated with advanced tumor stage and poor survival. GID2 promotes cell growth in vitro and tumor growth in vivo, and interacts with CDKN3 to regulate its expression and ubiquitination. Inhibition of CDKN3 reverses the promoting effects of GID2 on pancreatic cancer progression. These findings suggest that the GID2/CDKN3 axis could be a potential therapeutic target for pancreatic cancer.
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Ana Catarina Ferreira, Brittany M. Hemmer, Sarah M. Philippi, Alejandro B. Grau-Perales, Jacob L. Rosenstadt, Hanxiao Liu, Jeffrey D. Zhu, Tatyana Kareva, Tim Ahfeldt, Merina Varghese, Patrick R. Hof, Joseph M. Castellano
Summary: The functional output of the hippocampus, which supports memory function, is regulated by cellular and molecular processes. This study reveals that TIMP2, a molecule highly expressed in the hippocampus, plays a role in cellular programs related to neurogenesis and dendritic spine turnover. Its loss leads to impairments in hippocampus-dependent memory. This research provides insights into the regulation of synaptic plasticity by TIMP2.
MOLECULAR PSYCHIATRY
(2023)
Article
Cardiac & Cardiovascular Systems
Alessio Lissoni, Paco Hulpiau, Tania Martins-Marques, Nan Wang, Geert Bultynck, Rainer Schulz, Katja Witschas, Henrique Girao, Maarten De Smet, Luc Leybaert
Summary: The research revealed that the activation of ryanodine receptors (RyRs) triggers unitary currents with a single-channel conductance of around 220 pS, which are significantly reduced by knocking down connexin 43 (Cx43). The study also showed that both RyR activation and intracellular Ca2+ elevation are necessary for the opening of Cx43 hemichannels.
CARDIOVASCULAR RESEARCH
(2021)
Article
Cell Biology
Yun-Fei Yang, Wu Yang, Zhi-Yin Liao, Yong-Xin Wu, Zhen Fan, Ai Guo, Jing Yu, Qiu-Nan Chen, Jiang-Hao Wu, Jing Zhou, Qian Xiao
Summary: The loss of skeletal muscle mass and function in age-related sarcopenia can affect the quality of life in the elderly. Mitochondrial dysfunction, apoptosis, and mitochondrial calcium have been identified as key factors in skeletal muscle aging. MICU3 may play a crucial role in promoting mitochondrial Ca2+ homeostasis, reducing oxidative stress and apoptosis, and restoring skeletal muscle mass and function, making it a potential therapeutic target in skeletal muscle aging.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Rishav Mitra, Gaiti Hasan
Summary: Recent studies have shown that store-operated Ca2+ entry plays an important role in regulating neuronal function in Drosophila and mouse, with changes in ion channel function observed in neurons when this entry is lost. These changes are specific to neuronal subtypes. Gene expression studies in the mouse brain have also revealed differences in the expression of genes involved in ER-store Ca2+ release and store-operated Ca2+ entry across different neuronal classes. Loss of store-operated Ca2+ entry in neurons affects neuronal gene expression profiles, including genes encoding ion channels. Further research is needed to understand the functional significance of store-operated Ca2+ entry in specific neuronal subtypes and in the context of neurodegenerative syndromes.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Editorial Material
Cell Biology
Sangam Rajak, Paul M. Yen, Rohit A. Sinha
Summary: Crinophagy, the intracellular degradation of hormone-containing secretory vesicles by lysosomes, plays a critical role in regulating hormone secretion. Inhibition of MTORC1 induces crinophagy-mediated degradation of glucagon, leading to decreased secretion in response to hypoglycemia, suggesting that modulating crinophagy could be a novel therapeutic strategy for endocrine and metabolic disorders.
Article
Neurosciences
Yuewen Chen, Zhenyan Xu, Jing Chen, Yue Qiu, Lin Yuan, Peng Liu, Jing Duan, Li Chen, Yu Chen
Summary: In the developing cortex, the distribution and assembly of the F-actin cytoskeleton and the function of coronin 2B play a crucial role in neuronal migration and proper cortical development. Coronin 2B is responsible for the transition from a multipolar to bipolar morphology during neuronal migration. Loss of coronin 2B leads to heterotopic accumulation of migrating neurons, reduced dendritic complexity, and aberrant neuronal activity.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Wendy A. Herbst, Weixian Deng, James A. Wohlschlegel, Jennifer M. Achiro, Kelsey C. Martin
Summary: By using nucleus-specific proteomic mapping in silenced and stimulated neurons, researchers revealed an understudied mechanism of nuclear proteome regulation: activity-dependent proteasome-mediated degradation. They found that the tumor suppressor protein PDCD4 undergoes rapid stimulus-induced degradation in the nucleus of neurons. This degradation of PDCD4 is crucial for normal activity-dependent transcription, impacting genes involved in synapse formation, remodeling, and transmission.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fu-Mei Duan, Li-Juan Fu, Yong-Heng Wang, Enoch Appiah Adu-Gyamfi, Ling-Ling Ruan, Zeng-Wei Xu, Shi-Quan Xiao, Xue-Mei Chen, Ying-Xiong Wang, Tai-Hang Liu, Yu-Bin Ding
Summary: The study revealed that THBS1 regulates the fusion of placental cells through the CD36-mediated cAMP signaling pathway, and its upregulation impairs placental formation leading to preeclampsia. Thus, THBS1 can serve as a therapeutic target for mitigating abnormal syncytialization and preeclampsia.
Article
Cardiac & Cardiovascular Systems
Soren Brandenburg, Jan Pawlowitz, Vanessa Steckmeister, Hariharan Subramanian, Dennis Uhlenkamp, Marina Scardigli, Mufassra Mushtaq, Saskia I. Amlaz, Tobias Kohl, Jorg W. Wegener, Demetrios A. Arvanitis, Despina Sanoudou, Leonardo Sacconi, Gerd Hasenfuss, Niels Voigt, Viacheslav O. Nikolaev, Stephan E. Lehnart
Summary: This study found constitutively elevated levels of cAMP at the axial tubule junctional compartments in atrial myocytes, sustained by increased adenylyl cyclase activity. This compartmentalized cAMP level drove the phosphorylation of RyR2 clusters and increased L-type Ca2+ current density at the junctional sites. Beta-adrenergic stimulation overcame the compartmentation of cAMP by activating non-junctional RyR2 clusters throughout the cell.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Christina M. Lucato, Michelle L. Halls, Lisa M. Ooms, Heng-Jia Liu, Christina A. Mitchell, James C. Whisstock, Andrew M. Ellisdon
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Biochemistry & Molecular Biology
Maria L. R. Hughes, Bonan Liu, Michelle L. Halls, Kylie M. Wagstaff, Rahul Patil, Tony Velkov, David A. Jans, Nigel W. Bunnett, Martin J. Scanlon, Christopher J. H. Porter
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Cell Biology
Dane D. Jensen, TinaMarie Lieu, Michelle L. Halls, Nicholas A. Veldhuis, Wendy L. Imlach, Quynh N. Mai, Daniel P. Poole, Tim Quach, Luigi Aurelio, Joshua Conner, Carmen Klein Herenbrink, Nicholas Barlow, Jamie S. Simpson, Martin J. Scanlon, Bimbil Graham, Adam McCluskey, Phillip J. Robinson, Virginie Escriou, Romina Nassini, Serena Materazzi, Pierangelo Geppetti, Gareth A. Hicks, Macdonald J. Christie, Christopher J. H. Porter, Meritxell Canals, Nigel W. Bunnett
SCIENCE TRANSLATIONAL MEDICINE
(2017)
Article
Biochemistry & Molecular Biology
Masaaki Sato, Dana S. Hutchinson, Michelle L. Halls, Sebastian G. B. Furness, Tore Bengtsson, Bronwyn A. Evans, Roger J. Summers
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Dane D. Jensen, Michelle L. Halls, Jane E. Murphy, Meritxell Canals, Fiore Cattaruzza, Daniel P. Poole, TinaMarie Lieu, Hon-Wai Koon, Charalabos Pothoulakis, Nigel W. Bunnett
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Cell Biology
Debbie Willoughby, Michelle L. Halls, Katy L. Everett, Antonio Ciruela, Philipp Skroblin, Enno Klussmann, Dermot M. F. Cooper
JOURNAL OF CELL SCIENCE
(2012)
Article
Cell Biology
Laura J. Ayling, Stephen J. Briddon, Michelle L. Halls, Gerald R. V. Hammond, Luis Vaca, Jonathan Pacheco, Stephen J. Hill, Dermot M. F. Cooper
JOURNAL OF CELL SCIENCE
(2012)
Review
Physiology
R. A. D. Bathgate, M. L. Halls, E. T. van der Westhuizen, G. E. Callander, M. Kocan, R. J. Summers
PHYSIOLOGICAL REVIEWS
(2013)
Article
Biochemistry & Molecular Biology
Srgjan Civciristov, Andrew M. Ellisdon, Ryan Suderman, Cindy K. Pon, Bronwyn A. Evans, Oded Kleifeld, Steven J. Charlton, William S. Hlavacek, Meritxell Canals, Michelle L. Halls
Review
Pharmacology & Pharmacy
Srgjan Civciristov, Michelle L. Halls
BRITISH JOURNAL OF PHARMACOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Srgjan Civciristov, Cheng Huang, Bonan Liu, Elsa A. Marquez, Arisbel B. Gondin, Ralf B. Schittenhelm, Andrew M. Ellisdon, Meritxell Canals, Michelle L. Halls
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Christopher J. Lupton, Charles Bayly-Jones, Laura D'Andrea, Cheng Huang, Ralf B. Schittenhelm, Hari Venugopal, James C. Whisstock, Michelle L. Halls, Andrew M. Ellisdon
Summary: NF1 mutations cause neurofibromatosis type 1 and various cancers. This study reveals the structure of NF1 homodimer and provides insights into its role in cellular proliferation and cancer, potentially offering new therapeutic opportunities for modulating the RAS pathway.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Anh T. N. Nguyen, Diep T. N. Nguyen, Huan Yee Koh, Jason Toskov, William MacLean, Andrew Xu, Daokun Zhang, Geoffrey I. Webb, Lauren T. May, Michelle L. Halls
Summary: The application of artificial intelligence in drug discovery for G protein-coupled receptors (GPCRs) is expanding rapidly. It can assist in understanding the actions of GPCRs, discovering new ligand-GPCR interactions, and predicting clinical responses. This article provides an overview of artificial intelligence concepts and its applications in different stages of GPCR drug discovery. The benefits and limitations of artificial intelligence are discussed, along with the potential for further development in assisting GPCR drug discovery.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Michelle L. Halls, Ross A. D. Bathgate, Steve W. Sutton, Thomas B. Dschietzig, Roger J. Summers
PHARMACOLOGICAL REVIEWS
(2015)