Article
Endocrinology & Metabolism
Eleni Georgiadou, Charanya Muralidharan, Michelle Martinez, Pauline Chabosseau, Elina Akalestou, Alejandra Tomas, Fiona Yong Su Wern, Theodoros Stylianides, Asger Wretlind, Cristina Legido-Quigley, Ben Jones, Livia Lopez-Noriega, Yanwen Xu, Guoqiang Gu, Nour Alsabeeh, Celine Cruciani-Guglielmacci, Christophe Magnan, Mark Ibberson, Isabelle Leclerc, Yusuf Ali, Scott A. Soleimanpour, Amelia K. Linnemann, Tristan A. Rodriguez, Guy A. Rutter
Summary: Mitofusin gene expression is essential for maintaining normal glucose metabolism in pancreatic beta-cells, but does not affect incretin signaling. These findings are important for understanding the roles of mitofusins in beta-cells, the potential contributions of altered mitochondrial dynamics to diabetes development, and the impact of incretins on this process.
Article
Multidisciplinary Sciences
Miriam Scarpa, Colin Molloy, Laura Jenkins, Bethany Strellis, Rebecca F. Budgett, Sarah Hesse, Louis Dwomoh, Sara Marsango, Gonzalo S. Tejeda, Mario Rossi, Zeshan Ahmed, Graeme Milligan, Brian D. Hudson, Andrew B. Tobin, Sophie J. Bradley
Summary: Current treatments for neurodegenerative diseases like Alzheimer's disease have shown limited effectiveness, but activating the M1 receptor could potentially restore memory and slow disease progression. Recent research suggests that minimizing adverse reactions associated with M1 receptor activation can be achieved by ensuring proper phosphorylation and arrestin-dependent signaling. This approach shows promise for developing next-generation M1 receptor ligands with reduced side effects and improved neuroprotection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Eunhee Kim, Dong Min Lee, Min Ji Seo, Hong Jae Lee, Kyeong Sook Choi
Summary: Paraptosis is a type of programmed cell death characterized by dilation of the endoplasmic reticulum and/or mitochondria. Ca2+ transport has been shown to play an important role in paraptosis induced by various agents, and perturbations of cellular proteostasis and ion homeostasis are believed to contribute critically to the process. The communication between the ER and mitochondria mediated by Ca2+ appears to be crucial in inducing paraptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Benjamin Cartes-Saavedra, Josefa Macuada, Daniel Lagos, Duxan Arancibia, Maria E. Andres, Patrick Yu-Wai-Man, Gyoergy Hajnoczky, Veronica Eisner
Summary: Autosomal Dominant Optic Atrophy (ADOA), caused by OPA1 mutations, affects Ca2+ homeostasis by modulating ER-mitochondria coupling, potentially contributing to the progression of ADOA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Nan Wang, Chong Wang, Hongyang Zhao, Yichun He, Beiwu Lan, Liankun Sun, Yufei Gao
Summary: The cooperation and antagonism between organelles within the cell play a crucial role in maintaining cellular homeostasis. The signaling crosstalk between the endoplasmic reticulum (ER) and mitochondria influences cell fate. Mitochondria-associated membranes (MAMs) are pivotal in regulating lipid synthesis, calcium homeostasis, ER-mitochondrial coordination, and death signal transduction, contributing to cell death mechanisms such as apoptosis.
Review
Pharmacology & Pharmacy
Huong T. M. Nguyen, Emma T. van der Westhuizen, Christopher J. Langmead, Andrew B. Tobin, Patrick M. Sexton, Arthur Christopoulos, Celine Valant
Summary: This review focuses on the drug discovery of M-1 receptor for the treatment of Alzheimer's disease and schizophrenia. Despite some progress, only a few drugs have reached clinical trials due to cholinergic adverse effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jonas Kilian, Marius Ozenil, Marlon Millard, Dorka Fuertoes, Verena Maisetschlaeger, Wolfgang Holzer, Wolfgang Wadsak, Marcus Hacker, Thierry Langer, Verena Pichler
Summary: Due to their important role in mediating physiological functions, finding subtype-selective ligands for muscarinic acetylcholine receptors (mAChRs) has been challenging. In this study, a series of 12 carbamates with the potential for blood-brain barrier permeation were identified through a docking campaign. Compound 2 showed high affinity for hM(1)R and selectivity against hM(2-5)R, making it a promising candidate for PET tracer development.
Article
Multidisciplinary Sciences
Shanliang Zheng, Dong Zhao, Guixue Hou, Song Zhao, Wenxin Zhang, Xingwen Wang, Li Li, Liang Lin, Tie-Shan Tang, Ying Hu
Summary: The study demonstrates the interaction between TMCO1 and iASPP in colon cancer, affecting tumor growth and cell apoptosis by modulating Ca2+ homeostasis. Intervention in the iASPP-TMCO1 axis can effectively inhibit tumor progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Mohammad A. Ghane, Wei Wei, Dina W. Yakout, Zachary D. Allen, Cassandra L. Miller, Bin Dong, Jenny J. Yang, Ning Fang, Angela M. Mabb
Summary: The study found that disrupting Arc protein ubiquitination enhances DHPG-induced ER-mediated Ca2+ release. This alteration is observed in all neuronal subregions except secondary branchpoints. Disruptions in Arc ubiquitination increase Arc interaction with the integral ER protein Calnexin.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
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)
Article
Biochemistry & Molecular Biology
Pamela Teneqexhi, Alina Khalid, Khalin E. Nisbett, Greeshma A. Job, William S. S. Messer Jr, Michael E. Ragozzino
Summary: The study investigated the effect of the M-1 muscarinic receptor agonist CDD-0102A on changes in striatal glutamate concentrations during stereotyped motor behavior in BTBR and B6 mice. The findings suggest that CDD-0102A treatment attenuates glutamate decreases and increases in the dorsolateral striatum and reduces grooming behavior in BTBR mice, while it potentiates glutamate decreases and increases and elevates grooming behavior in B6 mice.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Xintong Bian, Ningke Fan, Meng Li, Daobin Han, Jia Li, Lu Fan, Xinyu Li, Liangsheng Kong, Hua Tang, Shijia Ding, Fangzhou Song, Siqiao Li, Wei Cheng
Summary: A hepatocellular carcinoma (HCC) cell-derived ER vesicle (ER-horse) has been developed for precise HCC nanotherapy by imitating the physiological function of endoplasmic reticulum (ER) and triggering excessive ER stress and apoptosis. The findings provide a new method for HCC nanotherapy via interference of ER stress signaling.
Article
Neurosciences
Alexander Joseph McDonald, David D. Mott
Summary: The study revealed that both pyramidal projection neurons (PNs) and inhibitory interneurons (INs) in the primate BNC express M1Rs, with a particularly high expression in PNs. The findings also showed that a significant portion of GAD-expressing INs in the BNC are also M1R positive, indicating the potential impact of M1R positive allosteric modulators in targeting both PNs and INs in the BNC.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Physiology
Lianguo Wang, Rachel C. Myles, I-Ju Lee, Donald M. Bers, Crystal M. Ripplinger
Summary: The study demonstrates that inhibition of SERCA can slow down SR Ca2+ reuptake, leading to an increase in the magnitude of Ca2+ alternans in cardiac cells, especially at fast pacing frequencies. Notably, the alternation of SR Ca2+ release precedes the alternation of SR Ca2+ load during rapid ventricular pacing.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Mika Naganawa, Nabeel Nabulsi, Shannan Henry, David Matuskey, Shu-Fei Lin, Lawrence Slieker, Adam J. Schwarz, Nancy Kant, Cynthia Jesudason, Kevin Ruley, Antonio Navarro, Hong Gao, Jim Ropchan, David Labaree, Richard E. Carson, Yiyun Huang
Summary: This study investigated the PET radiotracer C-11-LSN3172176 for M1 muscarinic acetylcholine receptors in healthy participants, finding that the 1TC and SRTM2 models are most suitable for quantitative analysis. The cerebellum was identified as a suitable reference region for the tracer. Overall, C-11-LSN3172176 demonstrated excellent test-retest reproducibility and holds promise for quantifying M1 receptors in the human brain.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Marc P. Lussier, Antonio Sanz-Clemente, Katherine W. Roche
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Xinglong Gu, Xia Mao, Marc P. Lussier, Mary Anne Hutchison, Liang Zhou, F. Kent Hamra, Katherine W. Roche, Wei Lu
NATURE COMMUNICATIONS
(2016)
Article
Cell Biology
Marc P. Lussier, Pascale K. Lepage, Simon M. Bousquet, Guylain Boulay
Article
Cell Biology
Pascale K. Lepage, Marc P. Lussier, Francois-Olivier McDuff, Pierre Lavigne, Guylain Boulay
Article
Neurosciences
Marc P. Lussier, Xinglong Gu, Wei Lu, Katherine W. Roche
EUROPEAN JOURNAL OF NEUROSCIENCE
(2014)
Article
Neurosciences
Marc P. Lussier, Yukiko Nasu-Nishimura, Katherine W. Roche
JOURNAL OF NEUROSCIENCE
(2011)
Article
Multidisciplinary Sciences
Marc P. Lussier, Bruce E. Herring, Yukiko Nasu-Nishimura, Albert Neutzner, Mariusz Karbowski, Richard J. Youle, Roger A. Nicoll, Katherine W. Roche
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2012)
Article
Neurosciences
Hou Ve, Valerie C. Cabana, Gilles Gouspillou, Marc P. Lussier
Article
Biochemistry & Molecular Biology
Kim Ghilarducci, Valerie C. Cabana, Camille Desroches, Kahina Chabi, Steve Bourgault, Laurent Cappadocia, Marc P. Lussier
Summary: Protein ubiquitination plays a role in various cellular functions beyond protein degradation. The study demonstrates the interaction between RNF167 and conjugating E2 enzymes, revealing submicromolar dissociation constants and providing insights into the mechanism of binding. Additionally, the research shows that GluA2 ubiquitination by UBE2N is possible only after priming by another conjugating E2 enzyme, shedding light on the ubiquitination process mediated by RNF167.
Review
Cell Biology
Valerie C. Cabana, Marc P. Lussier
Summary: The ubiquitin-proteasome system plays a fundamental role in biology by regulating proteostasis and cellular processes. E3 ubiquitin ligases, such as the RING subset, are involved in various cellular mechanisms and are associated with both physiological and pathological conditions, including cancer and neurological disorders. This review focuses on the structure, partners, and functions of the RING subset E3 ligases and discusses their association with pathophysiological conditions, such as cancer, asthma, and rare genetic disorders.
Article
Cell Biology
Valerie C. Cabana, Antoine Y. Bouchard, Audrey M. Senecal, Kim Ghilarducci, Said Kourrich, Laurent Cappadocia, Marc P. Lussier
Summary: Developmental and epileptic encephalopathies (DEE) are rare neurological disorders characterized by severe epilepsy and developmental delay. A recent study linked DEE73 with genetic alterations of the RNF13 gene, showing that these mutations affect the cellular and molecular mechanisms related to endosomal vesicle size and lysosomal localization. The study suggests that RNF13 variants disrupt association with the AP-3 complex, leading to changes in endosomal vesicle size and lysosomal localization.
Article
Biochemistry & Molecular Biology
Kim Ghilarducci, Valerie C. Cabana, Ali Harake, Laurent Cappadocia, Marc P. Lussier
Summary: This study identified a new ubiquitin ligase RNF167 for Rab7 and revealed the importance of Rab7's GTP-binding activity in membrane localization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Noe Quittot, Phuong Trang Nguyen, Armelle Tchoumi Neree, Marc P. Lussier, Steve Bourgault
BIOCHEMICAL JOURNAL
(2017)
Article
Biochemistry & Molecular Biology
Pascale K. Lepage, Marc P. Lussier, Hector Barajas-Martinez, Simon M. Bousquet, Alexandre P. Blanchard, Nancy Francoeur, Robert Dumaine, Guylain Boulay
JOURNAL OF BIOLOGICAL CHEMISTRY
(2006)