Article
Microbiology
Clem Marsilia, Mrinalini Batra, Irina D. Pokrovskaya, Changqi Wang, Dale Chaput, Daria A. Naumova, Vladimir V. Lupashin, Elena S. Suvorova
Summary: This study reveals the expanded function of the conservative Golgi tethering COG complex in T. gondii and identifies additional regulators of transport specific to the parasite, providing insights into the parasite's secretory organelles.
Review
Cell Biology
Shin Hye Noh, Ye Jin Kim, Min Goo Lee
Summary: This article summarizes the multiple pathways involved in the secretion of cellular proteins and focuses on the unconventional protein secretion (UPS) pathways related to autophagy. By describing and comparing different features, the role and mechanisms of autophagy in the transport of secretory cargos, including leaderless soluble proteins and Golgi-bypassing transmembrane proteins, are revealed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Farhana Taher Sumya, Irina D. Pokrovskaya, Zinia D'Souza, Vladimir V. Lupashin
Summary: This study used the auxin-inducible acute degradation system to investigate initial defects resulting from COG dysfunction. The results showed that acute COG inactivation caused a massive accumulation of CCD vesicles carrying Golgi enzymes and proteins. Different Golgi residents were segregated into different populations of CCD vesicles. This study provided a detailed view of primary cellular defects associated with COG dysfunction in human cells.
Article
Biochemistry & Molecular Biology
Alexander A. Mironov, Maksim A. Savin, Anna V. Zaitseva, Ivan D. Dimov, Irina S. Sesorova
Summary: The blood group system is based on the A or B antigens located on the surface of blood cells and is synthesized using unique Golgi glycosylation enzymes. Antibodies are produced against antigens of different blood groups. There are several hypotheses explaining the formation of these antibodies, including natural antibodies, gut bacteria-derived antibodies, and antibodies formed due to glycosylation mistakes or de-sialylation. Further research is needed to determine which hypothesis is correct.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marie-Estelle Losfeld, Ernesto Scibona, Chia-wei Lin, Markus Aebi
Summary: Glycoprotein processing is a complex and compartmentalized pathway in eukaryotic cells. We studied the kinetics of glycan processing of a model protein and developed a mathematical model of the secretory pathway. Our model revealed the importance of phosphorylated glycan structures in lysosomal sorting and showed that the model protein can take different routes of the cellular secretory pathway, resulting in increased glycan complexity of the secreted protein.
Article
Biology
Anitha P. Govind, Okunola Jeyifous, Theron A. Russell, Zola Yi, Aubrey Weigel, Abhijit Ramaprasad, Luke Newell, William Ramos, Fernando M. Valbuena, Jason C. Casler, Jing-Zhi Yan, Benjamin S. Glick, Geoffrey T. Swanson, Jennifer Lippincott-Schwartz, William N. Green
Summary: Increased neuronal activity leads to changes in N-glycan structures on dendritic surface glycoproteins, which are mediated by the growth and proliferation of Golgi satellites. These Golgi satellites act as distal glycosylation stations, impacting the dendritic surface and potentially influencing synaptic plasticity and diseases.
Article
Multidisciplinary Sciences
Maria Schwarz, Caroline E. Meyer, Alina Loeser, Kristina Lossow, Julian Hackler, Christiane Ott, Susanne Jaeger, Isabelle Mohr, Ella A. Eklund, Angana A. H. Patel, Nadia Gul, Samantha Alvarez, Ilayda Altinonder, Clotilde Wiel, Maria Maares, Hajo Haase, Anetta Haertlova, Tilman Grune, Matthias B. Schulze, Tanja Schwerdtle, Uta Merle, Hans Zischka, Volkan I. Sayin, Lutz Schomburg, Anna P. Kipp
Summary: Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P and its transport from the liver, while copper levels affect the release and transport of selenoprotein P, potentially impacting selenium transport to peripheral organs.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jule Truberg, Laura Hobohm, Alexander Jochimsen, Christine Desel, Michaela Schweizer, Matthias Voss
Summary: This study investigates the regulation and localization of Golgi enzymes by an intramembrane protease called SPPL3. The findings suggest that SPPL3 is predominantly located in the mid-Golgi and co-localizes with its substrates and non-substrate type II proteins. These results have important implications for understanding the role of SPPL3 in the regulation of Golgi glycosylation machinery.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Cell Biology
Zinia D'Souza, Farhana Taher Sumya, Amrita Khakurel, Vladimir Lupashin
Summary: The Golgi is the central organelle of the secretory pathway housing majority of the glycosylation machinery. Vesicular trafficking machinery plays a major role in coordinating Golgi trafficking for achieving Golgi homeostasis. Mutations in various components of glycosylation machinery can cause congenital disorders of glycosylation (CDG) with varying severities.
Review
Biochemistry & Molecular Biology
Nicholas D. Serra, Meera Sundaram
Summary: Transcytosis is a specialized form of transport where extracellular cargo is endocytosed, transported through the cytoplasm in vesicles, and secreted at a different plasma membrane surface. It allows membrane-impermeable macromolecules to pass through cells and become accessible to adjacent cells and tissues. Moreover, transcytosis also plays a role in redistributing plasma membrane proteins and lipids to different regions of the cell surface.
Article
Biochemistry & Molecular Biology
Dorothee Vicogne, Nicolas Beauval, Zoe Durin, Delphine Allorge, Kateryna Kondratska, Aurelien Haustrate, Natasha Prevarskaya, Vladimir Lupashin, Dominique Legrand, Francois Foulquier
Summary: TMEM165 is a cation transporter critical for Golgi glycosylation and cellular manganese homeostasis. Its deficiency leads to glycosylation defects, which can be restored by manganese supplementation. This study reveals the importance of TMEM165 in maintaining Golgi manganese homeostasis and cellular manganese detoxification through the activity of SPCA1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Cell Biology
Xiaoyan Zhang
Summary: The Golgi apparatus serves as a major processing station in the cell and requires a well-organized structure for proper protein glycosylation. Altered glycosylation is a hallmark of most cancer cells, and Golgi structural proteins are associated with tumor progression. Understanding Golgi structural and functional defects may help determine whether glycosylation defect is a cause or effect of oncogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mathieu Pottier, Van Anh Le Thi, Catherine Primard-Brisset, Jessica Marion, Michele Wolf Bianchi, Cindy Victor, Annabelle Dejardin, Gilles Pilate, Sebastien Thomine
Summary: The study finds that there are two copies of NRAMP3 metal transporters in the poplar genome, one of which retains the original function of releasing metals stored in vacuoles in Arabidopsis, while the other copy has acquired a new function in controlling the cell-to-cell transport of manganese in the Trans-Golgi Network. This research provides a clear case of neofunctionalization through a change in the subcellular localization of a metal transporter and evidence for the involvement of the secretory pathway in the cell-to-cell transport of manganese.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Review
Biochemistry & Molecular Biology
Reem Abouward, Giampietro Schiavo
Summary: Localisation of mRNA plays a crucial role in establishing and maintaining cellular polarity, synaptic plasticity, and other biological processes. Recent discoveries regarding RNA hitchhiking on cytoplasmic organelles have significant implications on our understanding of neuronal function in development, adulthood, and neurodegeneration. The mechanisms controlling mRNA localisation are largely conserved across evolution and have been extensively studied in various biological models.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Endocrinology & Metabolism
Ruizhi Duan, Dana Marafi, Zhi-Jie Xia, Bobby G. Ng, Reza Maroofian, Farhana Taher Sumya, Ahmed K. Saad, Haowei Du, Jawid M. Fatih, Jill V. Hunter, Hasnaa M. Elbendary, Shahid M. Baig, Uzma Abdullah, Zafar Ali, Stephanie Efthymiou, David Murphy, Tadahiro Mitani, Marjorie A. Withers, Shalini N. Jhangiani, Zeynep Coban-Akdemir, Daniel G. Calame, Davut Pehlivan, Richard A. Gibbs, Jennifer E. Posey, Henry Houlden, Vladimir V. Lupashin, Maha S. Zaki, Hudson H. Freeze, James R. Lupski
Summary: In this study, we report two homozygous missense variants in the COG3 gene that co-segregate with COG3-CDG phenotype. The affected individuals exhibit clinical manifestations such as global developmental delay, severe intellectual disability, microcephaly, and facial dysmorphism.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Cell Biology
Jacob A. McPhail, John E. Burke
Summary: Lipid phosphoinositides play important roles as signaling molecules and markers of organelle identity in eukaryotic cells. Viruses can manipulate the kinases and phosphatases involved in phosphoinositide generation for their replication. This review focuses on PI4KA and PI4KB, discussing their roles in signaling, membrane trafficking, and virus manipulation. The molecular mechanisms by which PI4KA and PI4KB are activated and usurped by viruses are also explored.
Review
Cell Biology
Giovanni D'Angelo, Gioele La Manno
Summary: The concept of lipotypes suggests that lipid composition plays a crucial role in regulating cell fate. Recent evidence indicates that lipid composition modulates cell response to signaling cues. The variability in cell lipid composition assists the divergence of differentiation trajectories, leading to the establishment of multiple cell identities.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Immunology
Zhirong Zhang, Rossella Venditti, Li Ran, Zengzhen Liu, Karl Vivot, Annette Schurmann, Juan S. Bonifacino, Maria Antonietta De Matteis, Romeo Ricci
Summary: The NLRP3 inflammasome plays a crucial role in the innate immune response, and disruption of the endoplasmic reticulum-endosome membrane contact sites (EECS) leads to NLRP3 accumulation in endosomes and activation of the inflammasome. Lowering endosomal phosphatidylinositol 4-phosphate (PI4P) levels prevents NLRP3 association with endosomes and inhibits inflammasome activation. This discovery helps us better understand the activation mechanism of the inflammasome.
Review
Biotechnology & Applied Microbiology
John E. Burke, Joanna Triscott, Brooke M. Emerling, Gerald R. Hammond
Summary: This Review describes the structure, function, regulation, and disease roles of clinically relevant PIKs outside of class I PI3Ks, as well as the development of potent and specific small-molecule inhibitors. Phosphoinositide kinases are master regulators of cellular processes and their dysregulation has been implicated in various human diseases. Recent years have seen increased interest in targeting phosphoinositide kinases beyond class I PI3Ks, leading to the clinical development of selective inhibitors. This comprehensive analysis provides an overview of the current understanding and progress in the development of phosphoinositide kinase inhibitors.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Ronja Reinhardt, Kai Hirzel, Gisela Link, Stephan A. Eisler, Tanja Hagele, Matthew A. H. Parson, John E. Burke, Angelika Hausser, Thomas A. Leonard
Summary: Phosphorylation is a common mechanism in cell signaling, and protein kinases are often regulated by phosphorylation. However, PKD regulates itself through dimerization-mediated trans-autoinhibition, followed by autophosphorylation, to control its activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Meredith L. Jenkins, Harish Ranga-Prasad, Matthew A. H. Parson, Noah J. Harris, Manoj K. Rathinaswamy, John E. Burke
Summary: The PIK3CA gene is frequently mutated in human cancer, and this study reveals the molecular mechanisms underlying the increased activity mediated by different oncogenic mutations in PIK3CA. Through a combination of biochemical assays and HDX-MS, the authors uncover unique regulatory mechanisms and explain how these mutations activate PI3K. This work has important implications for the development of mutant selective inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Sara La Manna, Valentina Roviello, Fabiana Napolitano, Anna Maria Malfitano, Vittoria Monaco, Antonello Merlino, Maria Monti, Konrad Kowalski, Lukasz Szczupak, Daniela Marasco
Summary: Three photoactivable metal-CORMs have been found to modulate the self-aggregation mechanism of the peptide covering the second helix of the C-terminal domain of nucleophosmin 1 in different ways, with two acting as aggregating agents and one as an anti-aggregating agent. This highlights the importance of ligand systems in the development of metal-based drugs with potential application as antiamyloidogenic agents.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ilaria Iacobucci, Bruno Hay Mele, Flora Cozzolino, Vittoria Monaco, Chiara Cimmaruta, Maria Monti, Giuseppina Andreotti, Maria Monticelli
Summary: Enzyme replacement therapy is the only option for Fabry patients with no AGAL activity, but it has limitations. This study explores two possible approaches to optimize the therapy: combining it with pharmacological chaperones and targeting AGAL interactors. The findings demonstrate that galactose can prolong AGAL half-life and provide a list of potential drugs that can affect enzyme replacement therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anyelo Duran, David A. Priestman, Macarena Las Heras, Boris Rebolledo-Jaramillo, Valeria Olguin, Juan F. Calderon, Silvana Zanlungo, Jaime Gutierrez, Frances M. Platt, Andres D. Klein
Summary: Using a systems genetics approach, we identified 30 shared predicted modifier genes between hepatic lysosomal enzymes and glycosphingolipids (GSLs), clustered in three pathways and associated with other diseases. Surprisingly, these genes are regulated by ten common transcription factors and miRNA-340p. These findings suggest novel therapeutic targets for Lysosomal Storage Disorders (LSDs) and indicate the potential involvement of GSL metabolism in other pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Henrik Nurmi, Anders P. E. Backman, Josefin Halin, Max Lonnfors, Tomas Blom, Pia Roos-Mattjus, Peter Mattjus
Summary: The glycolipid transfer protein (GLTP) is involved in various cellular processes, including lipid transport, sensing and regulating glycosphingolipid homeostasis, and facilitating vesicular transport. Knocking out GLTP in HeLa cells affected motility, three-dimensional growth, and cellular metabolism. The interaction between GLTP and VAP-A is important for cell adhesion, cohesion, and three-dimensional growth, and GLTP expression directly impacts vesicular trafficking.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alexandria L. Shaw, Matthew A. H. Parson, Linda Truebestein, Meredith L. Jenkins, Thomas A. Leonard, John E. Burke
Summary: Akt is a key regulator of cell growth signaling and its hyperactivation is oncogenic. This study used hydrogen deuterium exchange mass spectrometry to investigate the conformational changes induced by Akt inhibitors. The findings provide valuable insights for designing targeted therapeutics against Akt.
Article
Cell Biology
Manoj K. Rathinaswamy, Meredith L. Jenkins, Benjamin R. Duewell, Xuxiao Zhang, Noah J. Harris, John T. Evans, Jordan T. B. Stariha, Udit Dalwadi, Kaelin D. Fleming, Harish Ranga-Prasad, Calvin K. Yip, Roger L. Williams, Scott D. Hansen, John E. Burke
Summary: This study investigates the activation mechanisms of phosphoinositide 3-kinase (PI3Ky) in immune cells. Using various experimental methods, the researchers identified molecular differences between the p110y-p84 and p110y-p101 complexes, which explain their differential membrane recruitment and activation by Ras and GPCRs. The findings provide key insights into the molecular basis of PI3Ky complex activation.
Article
Cell Biology
Justine Hadjerci, Anne Billet, Pascal Kessler, Gilles Mourier, Marine Ghazarian, Anthony Gonzalez, Christian Wunder, Nesrine Mabrouk, Eric Tartour, Denis Servent, Ludger Johannes
Summary: Many molecular targets for cancer therapy are located in the cytosol, but therapeutic macromolecules generally cannot spontaneously translocate across membranes to reach these targets. To enhance cytosolic delivery, researchers have used Shiga toxin B-subunit (STxB) to deliver therapeutic principles to disease-relevant cells expressing its receptor, Gb3. By introducing unnatural amino acids and functionalizing them with hydrophobic entities, the membrane translocation of STxB was increased by a factor of 2.5, opening up new biomedical opportunities.
Editorial Material
Cell Biology
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan
Article
Medicine, Research & Experimental
Charlotte Gehin, Museer A. Lone, Winston Lee, Laura Capolupo, Sylvia Ho, Adekemi M. Adeyemi, Erica H. Gerkes, Alexander P. A. Stegmann, Estrella Lopez-Martin, Eva Bermejo-Sanchez, Beatriz Martinez-Delgado, Christiane Zweier, Cornelia Kraus, Bernt Popp, Vincent Strehlow, Daniel Graefe, Ina Knerr, Eppie R. Jones, Stefano Zamuner, Luciano A. Abriata, Vidya Kunnathully, Brandon E. Moeller, Anthony Vocat, Samuel Rommelaere, Jean-Philippe Bocquete, Evelyne Ruchti, Greta Limoni, Marine Van Campenhoudt, Samuel Bourgeat, Petra Henklein, Christian Gilissen, Bregje W. van Bon, Rolph Pfundt, Marjolein H. Willemsen, Jolanda H. Schieving, Emanuela Leonardi, Fiorenza Soli, Alessandra Murgia, Hui Guo, Qiumeng Zhang, Kun Xia, Christina R. Fagerberg, Christoph P. Beier, Martin J. Larsen, Irene Valenzuela, Paula Fernandez-alvarez, Shiyi Xiong, Robert Smigiel, Vanesa Lopez-Gonzalez, Lluis Armengol, Manuela Morleo, Angelo Selicorni, Annalaura Torella, Moira Blyth, Nicola S. Cooper, Valerie Wilson, Renske Oegema, Yvan Herenger, Aurore Garde, Ange-Line Bruel, Frederic Tran Mau-Them, Alexis B. R. Maddocks, Jennifer M. Bain, Musadiq A. Bhat, Gregory Costain, Peter Kannu, Ashish Marwaha, Neena L. Champaigne, Michael J. Friez, Ellen B. Richardson, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Yask Gupta, Tze Y. Lim, Simone Sanna-Cherchi, Bruno Lemaitre, Toshiyuki Yamaji, Kentaro Hanada, John E. Burke, Ana Marjia Jaksic, Brian D. McCabe, Paolo De Los Rios, Thorsten Hornemann, Giovanni D'Angelo, Vincenzo A. Gennarino
Summary: By studying individuals with de novo missense variants in CERT1, it was found that CERT autoregulation plays a central role in the control of sphingolipid biosynthetic flux. Inhibiting CERT pharmacologically can correct the morphological and motor abnormalities in CerTra syndrome, suggesting a potential therapeutic approach for patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)