Review
Cell Biology
Borui Li, Yi Qin, Xianjun Yu, Xiaowu Xu, Wenyan Yu
Summary: Lipid rafts are specialized membrane domains enriched with cholesterol and sphingolipids, regulating signal receptors to promote signaling cascades important in cancer cell survival, death, and metastasis. The concept of CASMER (cluster of apoptotic signaling molecule-enriched rafts) contributed by F. Mollinedo and C. Gajate highlights the role of lipid rafts in cancer progression, making them potential targets for cancer therapy.
CELL PROLIFERATION
(2022)
Article
Immunology
Joy Edwards-Hicks, Petya Apostolova, Joerg M. Buescher, Hannes Maib, Michal A. Stanczak, Mauro Corrado, Ramon I. Klein I. Geltink, Maria Elena Maccari, Matteo Villa, Gustavo E. Carrizo, David E. Sanin, Francesc Baixauli, Beth Kelly, Jonathan D. Curtis, Fabian Haessler, Annette Patterson, Cameron S. Field, George Caputa, Ryan L. Kyle, Melanie Soballa, Minsun Cha, Harry Paul, Jacob Martin, Katarzyna M. Grzes, Lea Flachsmann, Michael Mitterer, Liang Zhao, Frances Winkler, David Ali Rafei-Shamsabadi, Frank Meiss, Bertram Bengsch, Robert Zeiser, Daniel J. Puleston, David O'Sullivan, Edward J. Pearce, Erika L. Pearce
Summary: The authors demonstrate the impact of metabolic alteration on the acyl chain composition on phosphoinositide-driven signaling in CD8(+) T cells. They find that naive T cells are rich in polyunsaturated phosphoinositides, while effector T cells predominantly have saturated fatty acyl chains. The different pools of phosphoinositides play distinct roles in initiating and sustaining effector function in CD8(+) T cell differentiation.
Article
Immunology
Giovanna Flores-Mendoza, Noe Rodriguez-Rodriguez, Rosa M. Rubio, Iris K. Madera-Salcedo, Florencia Rosetti, Jose C. Crispin
Summary: The study revealed that Fas and FasL play an important role in the downregulation of CD8 cells induced by self-antigens, maintaining CD8 expression. The signaling of Fas/FasL is crucial for sustaining CD8 expression during repetitive antigen stimulation and encounters with self-antigens.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Yanrui Zhang, Taian Jin, Zhangqi Dou, Boxing Wei, Buyi Zhang, Chongran Sun
Summary: The binding of CD95 to CD95L triggers a cascade of signals leading to apoptosis, but most tumor cells are resistant to CD95L-induced apoptosis. In some cancers, the CD95-CD95L binding promotes tumor growth. This review summarizes the potential mechanisms of non-apoptotic signaling and the expression of CD95L in other cell types.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Oskar Staufer, Jochen Estebano Hernandez Buecher, Julius Fichtler, Martin Schroeter, Ilia Platzman, Joachim P. Spatz
Summary: Extracellular vesicles (EVs) play a fundamental role in the proper physiological functioning of multicellular organisms by shuttling nucleic acids and proteins between cells to regulate a plethora of cellular processes, especially immune signalling. In this study, the authors investigate vesicle-induced receptor sequestration (VIRS) as a universal mechanism that enhances the signalling potency of proteins presented on EV membranes. They propose that vesicle-triggered local clustering of membrane receptors is the principle structural mechanism underlying EV-based protein presentation.
Article
Biology
Benoit Boulan, Charlotte Ravanello, Amandine Peyrel, Christophe Bosc, Christian Delphin, Florence Appaix, Eric Denarier, Alexandra Kraut, Muriel Jacquier-Sarlin, Alyson Fournier, Annie Andrieux, Sylvie Gory-Faure, Jean-Christophe Deloulme
Summary: Neurodevelopmental axonal pathfinding plays a crucial role in brain wiring and cognitive abilities. Sema3E, through its interaction with MAP6 and CRMP4, is shown to be important in promoting axonal growth and development of the fornix. The study highlights the role of CRMP4 in transducing Sema3E signaling and its importance in understanding psychiatric diseases affecting the fornix.
Article
Multidisciplinary Sciences
Orie Tajima, Yuki Fujita, Yuhsuke Ohmi, Koichi Furukawa, Keiko Furukawa
Summary: Gangliosides, specifically GM3, have been found to play a role in insulin resistance and the regulation of insulin signaling in liver. In this study, double knockout mice lacking all gangliosides except GM3 were resistant to high fat diet-induced hepatosteatosis, and exhibited down-regulation of insulin signaling components. Hepatocytes expressing GM3 showed attenuated activation of downstream components compared to those expressing GM2. These findings suggest that the shift from GM2 to GM3 may suppress lipogenesis through attenuation of insulin signaling in mouse hepatocytes, providing protection against high fat diet-induced hepatosteatosis.
Article
Cell Biology
Koshu Okubo, Michael D. Brenner, Xavier Cullere, Gurpanna Saggu, Myra L. Patchen, Nandita Bose, Saki Mihori, Zhou Yuan, Clifford A. Lowell, Cheng Zhu, Tanya N. Mayadas
Summary: The fungal-derived beta-glucan binds to glycosphingolipid LacCer, reducing the affinity of FcγRIIA for IgG and inhibiting neutrophil recruitment to immunocomplexes. This inhibition pathway involves Lyn and SHP-1 signaling, providing a potential target for modulating immune responses.
Article
Biochemical Research Methods
Amy Ryan, Gerald R. V. Hammond, Alexander Deiters
Summary: The study introduces a highly efficient method for optical control of protein localization through site-specific incorporation of a photocaged amino acid. It has been shown to be applicable to different proteins and can rapidly activate cellular signaling pathways.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Cell Biology
Gael Galli, Pierre Vacher, Bernhard Ryffel, Patrick Blanco, Patrick Legembre
Summary: The study of CD95-mediated signaling pathways is significant, and previous research has identified numerous factors involved. However, due to the dynamic nature of protein-protein interactions and their occurring in various cellular locations, it is difficult to predict the specific cellular outcomes associated with CD95 engagement. CD95 stimulation can lead to apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways. Recent data suggests that CD95 may also activate pattern recognition receptors that sense damage-associated molecular patterns, potentially contributing to inflammation and cancer development or severity of chronic inflammatory and autoimmune disorders.
Article
Nanoscience & Nanotechnology
Bing Song, Rui Gao, Xiaohui Xu, Weijun Yan
Summary: In this study, a rat model of orthodontic recurrence was constructed and intervened with coptisine. The analysis of relevant indicators showed that coptisine can regulate the health status of periodontal tissue after orthodontics and reduce the occurrence of periodontal tissue inflammation. Further experiments confirmed that coptisine inhibits the activation of the Fas/FasL signaling pathway to prevent inflammation during orthodontic relapse.
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
(2023)
Article
Oncology
Beiyuan Hu, Tiantian Zou, Wei Qin, Xiaotian Shen, Yinghan Su, Jianhua Li, Yang Chen, Ze Zhang, Haoting Sun, Yan Zheng, Chao-Qun Wang, Zhengxin Wang, Tian-En Li, Shun Wang, Le Zhu, Xufeng Wang, Yan Fu, Xudong Ren, Qiongzhu Dong, Lun-Xiu Qin
Summary: Lenvatinib, a first-line treatment for hepatocellular carcinoma (HCC), has limited clinical benefits. This study reveals that HCC cells develop resistance to Lenvatinib by activating the EGFR-STAT3-ABCB1 pathway. Combined treatment with erlotinib, an EGFR inhibitor, may overcome acquired resistance and improve the clinical benefit of Lenvatinib.
Review
Cell Biology
Rosa Vona, Elisabetta Iessi, Paola Matarrese
Summary: Cholesterol is crucial for cell membrane structure and plays a key role in regulating cell signaling pathways. Its homeostasis is tightly regulated and dysregulation may be linked to cardiovascular diseases and cancer development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Parasitology
Natsuki Watanabe, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki
Summary: Phosphatidylinositol phosphates (PIPs) play pivotal roles in cellular events, with PIPs and PIP binding proteins in Entamoeba histolytica being involved in virulence-associated mechanisms. In silico survey of the E. histolytica genome using validated PIP-binding domain probes identified FYVE and PH domain containing proteins as the most expanded families in this organism.
PARASITOLOGY INTERNATIONAL
(2021)
Article
Cell Biology
Sijun Liu, Jun Tao, Fengqi Duan, Huangjing Li, Hongmei Tan
Summary: Lipid rafts play important roles in HHcy-accelerated AS. HHcy promotes lipid raft clustering via upregulation of ASM, which mediates the assembly of the NOX complex, causing an increase in ROS generation, NLRP3 inflammasome activation, and pyroptosis.
Article
Cell Biology
Yanfang Chen, Romane Leboutet, Celine Largeau, Siham Zentout, Christophe Lefebvre, Agnes Delahodde, Emmanuel Culetto, Renaud Legouis
Summary: Acute heat stress affects the development of Caenorhabditis elegans larvae without causing lethality or sterility, with mitochondrial fragmentation and autophagic flux playing key roles in developmental recovery. The adaptation to heat stress is independent of specific proteins and receptors, with mitochondria serving as a major site for autophagosome biogenesis. DRP-1 is involved in coordinating mitochondrial fission and autophagosome formation in stress conditions.
JOURNAL OF CELL BIOLOGY
(2021)
Editorial Material
Cell Biology
Yanfang Chen, Emmanuel Culetto, Renaud Legouis
Summary: Temperature variations can pose different challenges to cell homeostasis, with heat stress leading to a range of responses from beneficial effects to necrotic cell death. In the nematode Caenorhabditis elegans, acute non-lethal heat stress induces fragmentation of mitochondria, triggers autophagy flux in multiple tissues, and modulates developmental plasticity. Mitochondria, particularly in the epidermis, have been identified as a major site for autophagosome biogenesis, with the protein DRP-1 playing a crucial role in coordinating mitochondrial fission and autophagy during stress adaptation.
Article
Cell Biology
Marc Scherlinger, Vivien Guillotin, Isabelle Douchet, Pierre Vacher, Andrea Boizard-Moracchini, Jean-Philippe Guegan, Anne Garreau, Nathalie Merillon, Agathe Vermorel, Emmanuel Ribeiro, Irene Machelart, Estibaliz Lazaro, Lionel Couzi, Pierre Duffau, Thomas Barnetche, Jean-Luc Pellegrin, Jean-Francois Viallard, Maya Saleh, Thierry Schaeverbeke, Patrick Legembre, Marie-Elise Truchetet, Helene Dumortier, Cecile Contin-Bordes, Vanja Sisirak, Christophe Richez, Patrick Blanco
Summary: This study identified a P-selectin-dependent pathway in patients with systemic lupus erythematosus (SLE) and validated it as a potential therapeutic avenue. Platelets from SLE patients interacted with Treg cells via the P-selectin/PSGL-1 axis, affecting Treg cell function and suppressing immune responses. Blocking P-selectin in a mouse model of SLE improved disease features, indicating its potential as a therapeutic target.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Obstetrics & Gynecology
Ludivine Dion, Maela Le Lous, Krystel Nyangoh Timoh, Jean Leveque, Alexis Arnaud, Charles Henri-Malbert, Fabrice Foucher, Karim Boudjema, Claude Bendavid, Cecile Vigneau, Patrick Legembre, David Val-Laillet, Vincent Lavoue
Summary: The study demonstrates that dual ovarian venous return is sufficient for graft viability and survival in uterine transplant, with potential benefits for reducing post-surgery morbidity in living donors and UT time for recipients.
JOURNAL OF GYNECOLOGY OBSTETRICS AND HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Yanfang Chen, Emmanuel Culetto, Renaud Legouis
Summary: There is a debate on the function of Drp1 in mitophagy, with some experiments supporting its necessity while others suggesting it is not required. This review discusses the potential functions of Drp1 in different tissues, organisms, and stress conditions, and addresses the discrepancies in experimental findings. The article also speculates on Drp1-independent mitochondrial fission mechanisms and noncanonical roles of Drp1 in modulating organelle contact sites during autophagosome formation.
Article
Multidisciplinary Sciences
Zhongshun Liu, Congwei Jiang, Zhangmengxue Lei, Sihan Dong, Linlin Kuang, Chenxu Huang, Ying Gao, Mu Liu, Hui Xiao, Patrick Legembre, Jae U. Jung, Huaping Liang, Xiaozhen Liang
Summary: Type I interferons (IFNs) are the first line of defense against invading pathogens. This study identified a previously unknown protein, PINLYP, that interacts with TBK1 to induce the production of type I IFN. Loss of PINLYP impaired the activation of IRF3 and the production of IFN induced by various viruses and Toll-like receptor ligands. Mice lacking PINLYP were more susceptible to lethal virus infection, highlighting the importance of PINLYP in the host defense against viral infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Muhammad Farooq, Melanie Simoes Eugenio, Claire Piquet-Pellorce, Sarah Dion, Celine Raguenes-Nicol, Kathleen Santamaria, Ghania Hounana Kara-Ali, Thibaut Larcher, Marie-Therese Dimanche-Boitrel, Michel Samson, Jacques Le Seyec
Summary: This study investigates the role of RIPK1 in NASH and finds that RIPK1 in hepatocytes limits the progression of liver fibrosis during NASH.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Cell Biology
Gael Galli, Pierre Vacher, Bernhard Ryffel, Patrick Blanco, Patrick Legembre
Summary: The study of CD95-mediated signaling pathways is significant, and previous research has identified numerous factors involved. However, due to the dynamic nature of protein-protein interactions and their occurring in various cellular locations, it is difficult to predict the specific cellular outcomes associated with CD95 engagement. CD95 stimulation can lead to apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways. Recent data suggests that CD95 may also activate pattern recognition receptors that sense damage-associated molecular patterns, potentially contributing to inflammation and cancer development or severity of chronic inflammatory and autoimmune disorders.
Review
Biochemistry & Molecular Biology
Francesca De Giorgi, Vladimir N. Uversky, Francois Ichas
Summary: The article discusses Lionel Penrose's invention of the first self-replicating mechanical device in 1957 and its function, as well as its relevance to the genesis and proliferation of amyloid fibrils. It also highlights the significance of studies on alpha-Synuclein and its similarities to prions, its fibrillization-prone domain, and its nature as an intrinsically disordered protein. Combining these discoveries with the concept of the Penrose machine, the article proposes an explanation for the emergence and spread of different alpha-Synuclein fibril strains in alpha-Synucleinopathies.
Review
Biochemistry & Molecular Biology
Gabriel Ichim, Benjamin Gibert, Sahil Adriouch, Catherine Brenner, Nathalie Davoust, Solange Desagher, David Devos, Svetlana Dokudovskaya, Laurence Dubrez, Jerome Estaquier, Germain Gillet, Isabelle Guenal, Philippe P. Juin, Guido Kroemer, Patrick Legembre, Romain Levayer, Stephen Manon, Patrick Mehlen, Olivier Meurette, Olivier Micheau, Bernar Mignotte, Florence Nguyen-Khac, Nikolay Popgeorgiev, Jean-Lu Poyet, Muriel Priault, Jean-Ehrlan Ricci, Franck B. Riquet, Santos A. Susin, Magal Suzanne, Pierre Vacher, Ludivine Walter, Bertran Mollereau
Summary: Since the Nobel Prize was awarded more than twenty years ago for discovering the core apoptotic pathway in C. elegans, researchers around the world have conducted extensive research on apoptosis and various other forms of regulated cell death. Although there are still many aspects of regulated cell death that need to be clarified in specific cell subtypes and disease conditions, the last decade has seen the description of multiple cell death modalities, some of which have been successfully used in clinical therapy. To keep research into cell death alive, francophone researchers from several institutions in France and Belgium established the French Cell Death Research Network (FCDRN), which is at the forefront of emerging topics in cell death research. These research efforts will enhance our mechanistic knowledge of regulated cell death and its therapeutic applications in the coming years.
Article
Cell Biology
Shoji F. Kenji, Keerthi Kurma, Brigitte Collet, Christelle Oblet, Laure Debure, Carmelo Di Primo, Laetitia Minder, Franck Verite, Yannic Danger, Mickael Jean, Aubin Penna, Nicolas Levoin, Patrick Legembre
Summary: CD95 is a death receptor that promotes oncogenesis through various molecular mechanisms. This receptor can undergo cleavage and modification in both cancer cells and normal cells, with the modified N-terminal region potentially regulating receptor aggregation and death signaling.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Eden Lebrault, Christelle Oblet, Keerthi Kurma, Nicolas Levoin, Robin Jeannet, Mickael Jean, Pierre Vacher, Patrick Legembre
Summary: This study investigates the stoichiometry of CD95L required for apoptotic and nonapoptotic signals. The researchers generated CD95L concatemers of different chemistries and found that a hexameric structure is best for triggering cell death, while a dimer is sufficient for inducing apoptotic response in CD95-sensitive cells. Interestingly, trimeric and hexameric forms are the only ones capable of implementing a potent Ca2+ response, indicating the requirement for both aggregation and conformation to activate the Ca2+ pathway.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Robin Bernard-Bloch, Eden Lebrault, Xiaofan Li, Aurelien Sutra Del Galy, Arlette Garcia, Christelle Doliger, Veronique Parietti, Patrick Legembre, Gerard Socie, Saoussen Karray
Summary: The study found that Fas ligand is increased in immune-mediated diseases, but the role of its expression on donor non-T cells has not been addressed. Using a mouse model, the researchers discovered that removing Fas ligand from donor T- and B-depleted bone marrow cells increased gut damage and mortality. They also found that soluble Fas ligand and IL-18 levels were drastically reduced in recipients of Fas ligand-deficient grafts, suggesting a link between Fas ligand and IL-18 production.
JOURNAL OF LEUKOCYTE BIOLOGY
(2023)
Article
Immunology
Ellen A. Tiffney, Janine L. Coombes, Patrick Legembre, Robin J. Flynn
Summary: The cleaved form of CD95L (cl-CD95L) promotes parasite replication in macrophages and increases arginase-1 levels mediated by the JAK/STAT signaling pathway. This study suggests that cl-CD95L may impact T. gondii infection by targeting host anti-parasite effectors.
MICROBES AND INFECTION
(2022)
Correction
Multidisciplinary Sciences
Nadine Khadra, Laurence Bresson-Bepoldin, Aubin Penna, Benjamin Chaigne-Delalande, Bruno Segui, Thierry Levade, Anne-Marie Vacher, Josy Reiffers, Thomas Ducret, Jean-Francois Moreau, Michael D. Cahalan, Pierre Vacher, Patrick Legembre
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)