Article
Immunology
Rowayna Shouib, Gary Eitzen
Summary: Airway epithelial cells can respond to pathogens and stimulants through cytokine and chemokine secretion, but excessive secretion can cause chronic inflammation and pulmonary disorders. We identified Cdc42 as an important signaling molecule that regulates cytokine production and release. Inhibiting or silencing Cdc42 affected the gene expression and secretion of specific cytokines, particularly IL-8 trafficking and secretion.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Zhenkang Wen, Sipeng Lin, Changchuan Li, Zhuji Ouyang, Zhong Chen, Shixun Li, Yuxi Huang, Wenqiang Luo, Zhongcan Zheng, Peidong Guo, Manyuan Kuang, Yue Ding
Summary: This study found that inhibiting p110 delta could reduce the inflammation caused by titanium particles, thereby alleviating osteolysis. Additionally, miR-92a and KLF4 also played important roles in suppressing the inflammatory response induced by titanium particles.
CELL DEATH DISCOVERY
(2022)
Article
Peripheral Vascular Disease
Karina Kinghorn, Amy Gill, Allison Marvin, Renee Li, Kaitlyn Quigley, Simcha Singh, Michaelanthony T. Gore, Ferdinand le Noble, Feilim Mac Gabhann, Victoria L. Bautch
Summary: This study investigates the trafficking and secretion process of sFLT1 in endothelial cells and identifies key trafficking components involved. The results demonstrate that clathrin is required for sFLT1 trafficking near the Golgi and involves multiple trafficking components. Additionally, the secretion of sFLT1 in cells has an impact on vessel sprouting.
Article
Biochemistry & Molecular Biology
Feifan Zhang, Dong Yang, Jingchen Li, Cuilian Du, Xinran Sun, Wanru Li, Fengwei Liu, Yiwei Yang, Yuhong Li, Lei Fu, Rena Li, Claire Xi Zhang
Summary: This study reveals the function of synaptotagmin-11 (Syt11) in microglial immune responses. Syt11 inhibits cytokine release through interactions with vps10p-tail-interactor-1a (vti1a) and vti1b.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kenneth Down, Augustin Amour, Niall A. Anderson, Nick Barton, Sebastien Campos, Edward P. Cannons, Cole Clissold, Maire A. Convery, John J. Coward, Kevin Doyle, Birgit Duempelfeld, Christopher D. Edwards, Michael D. Goldsmith, Jana Krause, David N. Mallett, Grant A. McGonagle, Vipulkumar K. Patel, James Rowedder, Paul Rowland, Andrew Sharpe, Srividya Sriskantharajah, Daniel A. Thomas, Douglas W. Thomson, Sorif Uddin, J. Nicole Hamblin, Edith M. Hessel
Summary: Optimization of binding mode, removal of harmful substances, enhancement of potency and selectivity led to the discovery of a low dose and rat-toxicity suitable PI3K delta inhibitor for further development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xue-Mei Zheng, Yuan-Si Chen, Yu-Juan Ban, Yu-Jie Wang, Yong-Xi Dong, Li Lei, Bing Guo, Jian-Ta Wang, Lei Tang, Hong-Liang Li, Ji-Quan Zhang
Summary: In this study, a series of substituted benzoxazole derivatives were designed and synthesized. The compound 18a showed higher inhibitory activity against PI3Kα and better anti-cancer effects, as well as improved selectivity and pharmacokinetic properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Zexi Yin, Xin Tian, Runying Zou, Xiangling He, Keke Chen, Chengguang Zhu
Summary: Activated phosphoinositide 3-kinase delta syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by acquired gene function mutation, with clinical phenotypes such as recurrent respiratory infections and lymphoproliferation. Regular follow-up of APDS patients is recommended to prevent secondary tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
F. C. Palazzo, R. Sitia, T. Tempio
Summary: In multicellular organisms, cells communicate through cognate interactions between membrane and secretory proteins. The folding of these proteins is assisted by chaperones and enzymes in the early secretory compartment (ESC), preventing their transport beyond the Golgi. Cells can selectively secrete certain ESC residents through differential intracellular distribution and release mechanisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Jingbo Zhang, Huimin Jiang, Songwen Lin, Deyu Wu, Hua Tian, Lin Jiang, Yiman Cui, Jing Jin, Xiaoguang Chen, Heng Xu
Summary: In this study, novel and selective PI3Kδ inhibitors were designed and synthesized, among which compound 6 showed significant anticancer activity in cellular and mouse models, making it a promising candidate for the treatment of B-cell malignancies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Luyao Qiu, Yanping Wang, Wenjing Tang, Qiuyun Yang, Ting Zeng, Junjie Chen, Xuemei Chen, Liang Zhang, Lina Zhou, Zhiyong Zhang, Yunfei An, Xuemei Tang, Xiaodong Zhao
Summary: This study reviewed the clinical features, immunological characteristics, treatment, and prognosis of Chinese pediatric patients with APDS. The study found that sinopulmonary infections and lymphoproliferation were the most common complications in this cohort, while autoimmunity was also frequently observed.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Byung-Jun Sung, Sung-Bin Lim, Won-Mo Yang, Jae Hyeon Kim, Rohit N. Kulkarni, Young-Bum Kim, Moon-Kyu Lee
Summary: This study reveals the essential role of ROCK1 in regulating glucose-stimulated insulin secretion and glucose homeostasis in pancreatic β-cells. ROCK1 acts as an upstream regulator of glycolytic pyruvate kinase signaling, and its deficiency impairs insulin secretion and glucose tolerance.
MOLECULAR METABOLISM
(2022)
Review
Cell Biology
Yuichi Wakana, Felix Campelo
Summary: Membrane trafficking plays a crucial role in processing and transporting proteins and lipids, as well as in establishing cell compartmentation and tissue organization. The focus of this review is on a specific membrane trafficking route from the trans-Golgi network to the cell surface, highlighting the role of PKD-dependent pathway and membrane contact sites in this process. Additionally, the discussion includes various signaling pathways involved in regulating membrane trafficking, such as those mediated by PKD, GPCRs, growth factors, metabolites, and mechanosensors.
Article
Hematology
Xuefei Zhao, Matthew Cooper, James V. Michael, Yanki Yarman, Aiden Baltz, J. Kurt Chuprun, Walter J. Koch, Steven E. McKenzie, Maurizio Tomaiuolo, Timothy J. Stalker, Li Zhu, Peisong Ma
Summary: The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been extensively studied, and this study provides the first evidence of its role in limiting platelet activation and regulating the hemostatic response to injury.
Article
Immunology
Jenna M. DeLuca, Maegan K. Murphy, Xin Wang, Timothy J. Wilson
Summary: Regulation of FCRL1 signaling plays a crucial role in modulating B cell development and antibody responses by inhibiting ERK activation. FCRL1 has the potential to regulate peripheral B cell tolerance, homeostasis, and activation through its role in suppressing ERK activation.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Chemistry, Physical
Xiaoniu Fang, Ya Gao, Chen Wang, Huimin Chen, Tong Zhu
Summary: This study combined MD simulations and binding affinity calculations to elucidate the interaction mechanism of different inhibitors towards PI3K subtypes, pointing out the critical roles of key residues, hydrophobic interactions, and hydrogen bonds in understanding binding selectivity. The findings can serve as a theoretical reference for the design of more promising selective inhibitors.
CHEMICAL PHYSICS LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Yizhuo Wang, Rishika Abrol, Jeffrey Y. W. Mak, Kaustav Das Gupta, Divya Ramnath, Denuja Karunakaran, David P. Fairlie, Matthew J. Sweet
Summary: HDAC7 is an important enzyme that regulates cellular and developmental processes through multiple mechanisms. It plays a crucial role in immune cells, osteoclasts, muscle, the endothelium, and the epithelium. HDAC7 regulates gene expression, cell proliferation, cell differentiation, and cell survival, thereby impacting development, angiogenesis, immune functions, inflammation, and metabolism.
Article
Biochemistry & Molecular Biology
Ramon Martinez-Marmol, Christopher Small, Anmin Jiang, Tishila Palliyaguru, Tristan P. Wallis, Rachel S. Gormal, Jean-Baptiste Sibarita, Jurgen Gotz, Frederic A. Meunier
Summary: This study reveals the important role of Fyn kinase in learning and memory, and its involvement in dementias. The P301L mutant Tau promotes abnormal clustering of Fyn in dendrites, and inhibition of Fyn's auto-inhibitory closed conformation increases its clustering. The ability of P301L Tau to form biomolecular condensates enhances Fyn clustering and signaling.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Kaustav Das Gupta, Divya Ramnath, Jessica B. von Pein, James E. B. Curson, Yizhuo Wang, Rishika Abrol, Asha Kakkanat, Shayli Varasteh Moradi, Kimberley S. Gunther, Ambika M. V. Murthy, Claudia J. Stocks, Ronan Kapetanovic, Robert C. Reid, Abishek Iyer, Zoe C. Ilka, William M. Nauseef, Manuel Plan, Lin Luo, Jennifer L. Stow, Kate Schroder, Denuja Karunakaran, Kirill Alexandrov, Melanie R. Shakespear, Mark A. Schembri, David P. Fairlie, Matthew J. Sweet
Summary: The cytoplasmic lysine deacetylase HDAC7 in macrophages acts as a metabolic switch, enabling the immune system to respond differently to various threats. It regulates glycolysis and the pentose phosphate pathway to trigger distinct immune responses to distal danger signals and proximal bacterial threats.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Syeda Farhana Afroz, Karoline D. Raven, Grace M. E. P. Lawrence, Ronan Kapetanovic, Kate Schroder, Matthew J. Sweet
Summary: Mitochondria serve as both the metabolic hub and the innate immune signaling and activation hub in macrophages. Macrophages use a variety of receptors and signaling molecules, with mitochondrial biology implicated in many responses. The balance between mitochondrial fission and fusion plays a crucial role in regulating macrophage functions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Editorial Material
Microbiology
Larisa I. Labzin, Kate Schroder
Summary: In this study, the authors investigate the cellular and molecular sources of elevated IL-10 and IL-6 in COVID-19. They find that immune cells sense SARS-CoV-2 infection in neighboring epithelial cells, triggering inflammasome signaling and release of IL-10, which promotes the release of IL-6.
CELL HOST & MICROBE
(2023)
Article
Biochemistry & Molecular Biology
Merja Joensuu, Parnayan Syed, Saber H. Saber, Vanessa Lanoue, Tristan P. Wallis, James Rae, Ailisa Blum, Rachel S. Gormal, Christopher Small, Shanley Sanders, Anmin Jiang, Stefan Mahrhold, Nadja Krez, Michael A. Cousin, Ruby Cooper-White, Justin J. Cooper-White, Brett M. Collins, Robert G. Parton, Giuseppe Balistreri, Andreas Rummel, Frederic A. Meunier
Summary: It has been found that botulinum neurotoxin type A (BoNT/A) targets nerve terminals by binding to two receptors on the neuronal plasma membrane: polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). The entry of BoNT/A into synaptic vesicles (SVs) requires a tripartite surface nanocluster, which consists of a preassembled PSG-synaptotagmin-1 (Syt1) complex and SV2 on the neuronal plasma membrane. This tripartite nanocluster controls the endocytic sorting of the toxin into synaptic vesicles.
Editorial Material
Cell Biology
Jennifer L. L. Stow, Matthew J. J. Sweet
Summary: The excessive phagocytosis of apoptotic cell corpses by macrophages in Drosophila embryos creates highly oxidative environments. A recent study by Clemente and Weavers (2023) reveals for the first time that macrophage Nrf2 is primed to sustain immune function and mitigate bystander oxidative damage.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Cell Biology
Yoshihiko Kuchitsu, Kojiro Mukai, Rei Uematsu, Yuki Takaada, Ayumi Shinojima, Ruri Shindo, Tsumugi Shoji, Shiori Hamano, Emari Ogawa, Ryota Sato, Kensuke Miyake, Akihisa Kato, Yasushi Kawaguchi, Masahiko Nishitani-Isa, Kazushi Izawa, Ryuta Nishikomori, Takahiro Yasumi, Takehiro Suzuki, Naoshi Dohmae, Takefumi Uemura, Glen N. N. Barber, Hiroyuki Arai, Satoshi Waguri, Tomohiko Taguchi
Summary: Stimulator of interferon genes (STING) is crucial for the immune response against DNA pathogens, and its degradation is mediated by endosomal sorting complexes required for transport (ESCRT) proteins. STING-positive vesicles derived from recycling endosomes are encapsulated into lysosomes after STING ubiquitination. This study provides insights into the regulation of STING and prevents hyperactivation of the immune response.
NATURE CELL BIOLOGY
(2023)
Article
Neurosciences
Adekunle T. Bademosi, Marianna Decet, Sabine Kuenen, Carles Calatayud, Jef Swerts, Sandra F. Gallego, Nils Schoovaerts, Spyridoula Karamanou, Nikolaos Louros, Ella Martin, Jean-Baptiste Sibarita, Katlijn Vints, Natalia V. Gounko, Frederic A. Meunier, Anastassios Economou, Wim Versees, Frederic Rousseau, Joost Schymkowitz, Sandra-F. Soukup, Patrik Verstreken
Summary: Neuronal activity-induced calcium influx is connected to synaptic autophagy and neuronal survival through Endophilin-A in a Parkinson disease-relevant fashion. Mutations in the disordered loop of Endophilin-A render it insensitive to neuronal stimulation, affecting protein dynamics and autophagosome formation. Balanced stimulation-induced autophagy is critical for dopaminergic neuron survival, and a variant in the human ENDOA1 disordered loop conferring risk to Parkinson disease also blocks nanodomain protein mobility and autophagy in vivo and in human-induced dopaminergic neurons.
Article
Biochemistry & Molecular Biology
Larisa I. Labzin, Keng Yih Chew, Kathrin Eschke, Xiaohui Wang, Tyron Esposito, Claudia J. Stocks, James Rae, Ralph Patrick, Helen Mostafavi, Brittany Hill, Teodor E. Yordanov, Caroline L. Holley, Stefan Emming, Svenja Fritzlar, Francesca L. Mordant, Daniel P. Steinfort, Kanta Subbarao, Christian M. Nefzger, Anne K. Lagendijk, Emma J. Gordon, Robert G. Parton, Kirsty R. Short, Sarah L. Londrigan, Kate Schroder
Summary: Macrophages are important cells in the development of COVID-19, and ACE2 receptors are only present on a subset of macrophages at infection sites. Research shows that ACE2-deficient macrophages do not replicate the virus or induce inflammatory cytokine expression, while ACE2-overexpressing macrophages can replicate and release the virus.
Article
Multidisciplinary Sciences
Tristan P. Wallis, Anmin Jiang, Kyle Young, Huiyi Hou, Kye Kudo, Alex J. McCann, Nela Durisic, Merja Joensuu, Dietmar Oelz, Hien Nguyen, Rachel S. Gormal, Frederic A. Meunier
Summary: Single-molecule localization microscopy techniques are essential for understanding the organization of protein clusters at the nanometer scale in living cells. In this study, the R-tree spatial indexing algorithm was used to determine the membership of individual molecular trajectories in nanoclusters. By extending the spatial indexing into the time dimension, spatiotemporal clusters were identified, revealing the dynamics of neuroexocytosis. The findings have been incorporated into a free and open-source Python graphic user interface called NASTIC.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Yue Zhang, He Xian, Ekaterina Strounina, Kimberley S. Gunther, Matthew J. Sweet, Chen Chen, Chengzhong Yu, Yue Wang
Summary: In this study, tetrasulphide bridged mesoporous organosilica nanoparticles (MONs) were found to have enhanced transfection performance of plasmid DNA (pDNA) in dendritic cell (DC) lines compared to conventional mesoporous silica nanoparticles (MSNs). This enhancement is attributed to the glutathione (GSH) depletion capability of MONs, which increases the activation of the mammalian target of rapamycin complex 1 (mTORc1) pathway and enhances translation and protein expression. The increased transfection efficiency was only observed in high GSH cell lines, validating the mechanism. This study provides a new design principle for nano delivery systems targeting pDNA delivery to DCs.
Article
Cell Biology
Kentaro Matsumoto, Shenwei Ni, Hiroyuki Arai, Takashi Toyama, Yoshiro Saito, Takehiro Suzuki, Naoshi Dohmae, Kojiro Mukai, Tomohiko Taguchi
Summary: Phenylarsine oxide (PAO) can activate mouse STING by covalently binding to cysteine residues, independent of cGAS or cGAMP. STING activation with PAO requires ER-to-Golgi trafficking and palmitoylation of STING. The study reveals that cysteine residues in STING can serve as a novel target for the development of STING agonists.
CELL STRUCTURE AND FUNCTION
(2023)
