Review
Cell Biology
P. Sahu, A. Balakrishnan, R. Di Martino, A. Luini, D. Russo
Summary: Tumorigenesis is associated with aberrant glycosylation, but the exact cause and mechanisms are still unclear. The levels and localization of glycosylation enzymes determine the glycosylation potential, and the cisternal maturation mechanism plays a key role in Golgi glycan synthesis. This mechanism is proposed to be a combination of pathways that control functionally related glycosylation enzymes. The identification of oncogenes among the cisternal maturation machinery provides insights into the regulation of aberrant glycosylation in cancer cells and potential targets for anticancer treatments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rotimi Fasimoye, Wentao Dong, Raja S. Nirujogi, Eshaan S. Rawat, Miharu Iguchi, Kwamina Nyame, Toan K. Phung, Enrico Bagnoli, Alan R. Prescott, Dario R. Alessi, Monther Abu-Remaileh
Summary: The Golgi is a crucial organelle involved in protein and lipid biosynthesis, as well as sorting and secretion. Dysfunctional Golgi is associated with various diseases. This study presents a Golgi immunoprecipitation technique to isolate intact Golgi mini-stacks for analysis. The analysis pipeline reveals the molecular features of the human Golgi, including proteome, metabolome, and lipidome profiles. This comprehensive molecular map provides a powerful method to study the Golgi in health and disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Manfei Li, Ran Zhao, Yanfang Du, Xiaomeng Shen, Qiang Ning, Yunfu Li, Dan Liu, Qing Xiong, Zuxin Zhang
Summary: This study characterized the AGAP-recruited complex and its roles in maize cellular physiology and agronomically important traits. The coordinated KNR6-AGAP-ARF1 complex modulates vegetative and reproductive traits by participating in vesicle trafficking in maize, providing insight into the regulation of inflorescence development, ear length, and kernel number in maize.
Article
Biochemistry & Molecular Biology
Galina Beznoussenko, Hee-Seok Kweon, Irina S. Sesorova, Alexander A. Mironov
Summary: This study compared the explanatory power of the cisterna maturation-progression model and the kiss-and-run model for the intra-Golgi transport. The authors found that their observations were more in line with the kiss-and-run model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Karen M. Page, Jessica J. McCormack, Mafalda Lopes-da-Silva, Francesca Patella, Kimberly Harrison-Lavoie, Jemima J. Burden, Ying-Yi Bernadette Quah, Dominic Scaglioni, Francesco Ferraro, Daniel F. Cutler
Summary: In this study, a hypothetical Golgi organization was validated against quantifiable secretory output. The best-fitting model suggests a highly dynamic ribbon structure with stable mini-stack dimers, capable of rapid rearrangement. This model indicates that the Golgi ribbon is more complex than generally thought.
Article
Reproductive Biology
Yue Wang, Chun-Hua Xing, Shun Chen, Shao-Chen Sun
Summary: The study showed that ZEN exposure disrupted organelle function in porcine oocyte meiotic maturation, affecting mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome.
Article
Biology
Alkesh Yadav, Quentin Vagne, Pierre Sens, Garud Iyengar, Madan Rao
Summary: In this article, a simplified chemical synthesis model is used to analyze the trade-offs between the number of cisternae, enzymes, and their specificity required to synthesize a prescribed target glycan distribution with high fidelity. The study shows that multiple cisternae and precise enzyme partitioning are necessary to synthesize complex glycan distributions observed in real cells. Additionally, there is an optimal level of enzyme specificity that achieves the target distribution accurately.
Article
Biochemistry & Molecular Biology
Riccardo Rizzo, Domenico Russo, Kazuo Kurokawa, Pranoy Sahu, Bernadette Lombardi, Domenico Supino, Mikhail A. Zhukovsky, Anthony Vocat, Prathyush Pothukuchi, Vidya Kunnathully, Laura Capolupo, Gaelle Boncompain, Carlo Vitagliano, Federica Zito Marino, Gabriella Aquino, Daniela Montariello, Petra Henklein, Luigi Mandrich, Gerardo Botti, Henrik Clausen, Ulla Mandel, Toshiyuki Yamaji, Kentaro Hanada, Alfredo Budillon, Franck Perez, Seetharaman Parashuraman, Yusuf A. Hannun, Akihiko Nakano, Daniela Corda, Giovanni D'Angelo, Alberto Luini
Summary: Research shows that a group of sequentially-acting enzymes in the Golgi bind to the oncogenic protein GOLPH3, affecting glycosphingolipid synthesis and cell proliferation by regulating enzyme localization and degradation rate. These findings reveal a novel oncogenic mechanism of action for GOLPH3 in glycosphingolipid metabolism.
Article
Physics, Multidisciplinary
Kiandokht Panjtan Amiri, Asa Kalish, Shankar Mukherji
Summary: Understanding the precision of cell assembly and maintenance of subcellular structures is a major challenge in cellular biophysics. This study demonstrates that cells can robustly control average fluctuations in organelle size and proposes a theoretical framework for organelle size control.
PHYSICAL REVIEW LETTERS
(2023)
Review
Cell Biology
Sarmistha Mahanty, Subba Rao Gangi Setty
Summary: Epidermal lamellar bodies (eLBs) are secretory organelles necessary for skin homeostasis, belonging to lysosome-related organelles (LROs) with a complex formation process related to other organelles. Disruption of the multistep biogenesis processes often occurs in skin disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Petia Adarska, Luis Wong-Dilworth, Francesca Bottanelli
Summary: Molecular switches of the ADP-ribosylation factor (ARF) GTPase family play crucial roles in coordinating intracellular trafficking, including membrane deformation, cargo sorting, and recruitment of downstream coat proteins and effectors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Plant Sciences
Cecilia Rodriguez-Furlan, Ariana Emami, Jaimie M. Van Norman
Summary: The polarity of plasma membrane proteins plays a crucial role in cell morphogenesis and plant development. In Arabidopsis root endodermal cells, the secretion machinery responsible for the polarized secretion of two transmembrane kinases, IRK and KOIN, was investigated. The researchers found that distinct mechanisms, mediated by specific ADP-ribosylation factor-guanine-nucleotide exchange factors (ARF-GEFs), guide the polarized secretion of these proteins, independent of cell type or polar axis.
Article
Biology
Divyanshu Mahajan, Hieng Chiong Tie, Lei Lu
Summary: This article successfully visualizes the cisternal organization of nocodazole-induced Golgi ministacks through a side-averaging approach coupled with Airyscan microscopy. The method is able to separate the top view and side view of disk-shaped ministacks in the Golgi complex and enhance the common structural features through image processing.
Article
Cell Biology
Justyna M. Meissner, Katarina Akhmetova, Tomasz Szul, Ekaterina G. Viktorova, Bingdong Sha, Jay M. Bhatt, Eunjoo J. Lee, Richard A. Kahn, George A. Belov, Igor Chesnokov, Elizabeth Sztul
Summary: In this study, we identified the essential role of the HDS3 domain in GBF1 membrane association in mammalian cells and its critical function during Drosophila melanogaster development. We characterized the interdomain arrangements of GBF1 by electron microscopy and proposed models for GBF1 engagement on the membrane.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Infectious Diseases
Yuko Shimamoto, Ruud H. J. Verstegen, Tomoyuki Mizuno, Tal Schechter, Upton Allen, Shinya Ito
Summary: This study evaluated the impact of augmented renal clearance (ARC) on vancomycin clearance in paediatric patients with febrile neutropenia following HSCT. It was found that children aged 6 months to 6 years with ARC may require an initial vancomycin dose up to 35%-65% higher than current dosing guidelines to achieve optimal target attainment.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Xiaonan Dong, Yuting Yang, Zhongju Zou, Yuting Zhao, Bo Ci, Lin Zhong, Madhura Bhave, Liwei Wang, Yi-Chun Kuo, Xiao Zang, Rui Zhong, Elizabeth R. Aguilera, R. Blake Richardson, Boris Simonetti, John W. Schoggins, Julie K. Pfeiffer, Li Yu, Xuewu Zhang, Yang Xie, Sandra L. Schmid, Guanghua Xiao, Paul A. Gleeson, Nicholas T. Ktistakis, Peter J. Cullen, Ramnik J. Xavier, Beth Levine
Summary: Autophagy plays a crucial role in immunity, especially in initiating autophagy during viral infection. SNX5 activates the PI3KC3 complex on endosomes to promote the initiation of autophagy, which is important for cellular defense against viral infections.
Article
Oncology
Zoe S. Walters, Ewa Aladowicz, Barbara Villarejo-Balcells, Gary Nugent, Joanna L. Selfe, Paul Eve, Julian Blagg, Olivia Rossanese, Janet Shipley
Summary: Rhabdomyosarcomas (RMS) are soft tissue sarcomas predominantly found in children, and current treatments have severe side effects and poor outcomes, necessitating the discovery of novel, more targeted therapies. High expression of histone demethylases, particularly KDM4B, supports proliferation of RMS cells, and sustained knockdown of KDM4B can lead to functional compensation by KDM4A. Targeting both KDM4A and KDM4B is shown to be effective in killing RMS cells and overcoming functional redundancy in order to elicit strong therapeutic responses.
Review
Rheumatology
Dibyendu Bhattacharyya, Maria E. Teves, John Varga
Summary: Primary cilia play a crucial role in the development of fibrosis, influencing the transition of mesenchymal progenitor cells to myofibroblasts. Recent studies have shown that alterations in primary cilia can impact the process of myofibroblast transition, suggesting potential new approaches for fibrosis prevention and treatment. Further research on the mechanisms involving primary cilia may provide valuable insights into the pathogenesis of fibrosis.
CURRENT OPINION IN RHEUMATOLOGY
(2021)
Article
Chemistry, Medicinal
Matthew G. Lloyd, Rosemary Huckvale, Kwai-Ming J. Cheung, Matthew J. Rodrigues, Gavin W. Collie, Olivier A. Pierrat, Mahad Gatti Iou, Michael Carter, Owen A. Davis, P. Craig McAndrew, Emma Gunnell, Yann-Vai Le Bihan, Rachel Talbot, Alan T. Henley, Louise D. Johnson, Angela Hayes, Michael D. Bright, Florence Raynaud, Mirco Meniconi, Rosemary Burke, Rob L. M. van Montfort, Olivia W. Rossanese, Benjamin R. Bellenie, Swen Hoelder
Summary: Optimization of modestly active starting points led to potent inhibitors of BCL6 by perturbing a water network and forming new interactions, ultimately achieving a 100-fold improvement in activity. The most potent compounds displaced three of the five initial water molecules and formed hydrogen bonds with the remaining two, showing promising inhibition of BCL6 in cells and satisfactory pharmacokinetic properties for compound 25.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Lin Bai, Bhawik K. Jain, Qinglong You, H. Diessel Duan, Mehmet Takar, Todd R. Graham, Huilin Li
Summary: This study reports the structure of the P4B ATPase Neo1 in several states, clarifying its substrate transport mechanism and revealing similar functional intermediate states to dimeric flippases. The findings suggest that evolutionarily distant P4 ATPases use a structurally conserved mechanism for substrate transport.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Rosemary Huckvale, Alice C. Harnden, Kwai-Ming J. Cheung, Olivier A. Pierrat, Rachel Talbot, Gary M. Box, Alan T. Henley, Alexis K. de Haven Brandon, Albert E. Hallsworth, Michael D. Bright, Hafize Aysin Akpinar, Daniel S. J. Miller, Dalia Tarantino, Sharon Gowan, Angela Hayes, Emma A. Gunnell, Alfie Brennan, Owen A. Davis, Louise D. Johnson, Selby de Klerk, Craig McAndrew, Yann-Vai Le Bihan, Mirco Meniconi, Rosemary Burke, Vladimir Kirkin, Rob L. M. van Montfort, Florence I. Raynaud, Olivia W. Rossanese, Benjamin R. Bellenie, Swen Hoelder
Summary: This study optimized a benzimidazolone molecular glue-type degrader, leading to the development of a highly potent probe CCT373566 for sustained depletion of BCL6. The research discovered a sharp degradation SAR and demonstrated the impact of subtle structural changes on the ability to induce degradation of BCL6. In a lymphoma xenograft mouse model, CCT373566 showed modest in vivo efficacy following oral dosing.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Owen A. Davis, Kwai-Ming J. Cheung, Alfie Brennan, Matthew G. Lloyd, Matthew J. Rodrigues, Olivier A. Pierrat, Gavin W. Collie, Yann-Vai Le Bihan, Rosemary Huckvale, Alice C. Harnden, Ana Varela, Michael D. Bright, Paul Eve, Angela Hayes, Alan T. Henley, Michael D. Carter, P. Craig McAndrew, Rachel Talbot, Rosemary Burke, Rob L. M. van Montfort, Florence Raynaud, Olivia W. Rossanese, Mirco Meniconi, Benjamin R. Bellenie, Swen Hoelder
Summary: A new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein was identified by ring fusion onto a quinolinone lead series. This was achieved by attaining close shape complementarity and a conformationally restricted core, resulting in potent BCL6 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Naini Chakraborty, Bhawik Kumar Jain, Samruddhi Shembekar, Dibyendu Bhattacharyya
Summary: This study investigates the potential functional link between ER-mitochondria encounter structures (ERMES) and ER exit sites (ERES). The disruption of either ERMES or ERES affects the other, and a chaperone protein, Djp1, is found to regulate mitochondrial protein import in the ERES-ERMES proximal region.
Article
Immunology
Bhawik K. Jain, Andrew S. Wagner, Todd B. Reynolds, Todd R. Graham
Summary: Candida albicans is a common cause of human mucosal yeast infections, and antifungal medications targeting the pathogen cell wall or plasma membrane have been effective. This study shows that the transport of glucosylceramide (GIcCer) and/or phosphatidylcholine (PC) by plasma membrane P4-ATPases is important for the pathogenicity of Candida albicans. The mutant strains lacking Dnf2 protein exhibit defects in yeast-to-hypha growth transition, filamentous growth, and virulence in systemically infected mice.
INFECTION AND IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Wenxia Wang, Swarna Bale, Jun Wei, Bharath Yalavarthi, Dibyendu Bhattacharyya, Jing Jing Yan, Hiam Abdala-Valencia, Dan Xu, Hanshi Sun, Roberta G. Marangoni, Erica Herzog, Sergejs Berdnikovs, Stephen D. Miller, Amr H. Sawalha, Pei-Suen Tsou, Kentaro Awaji, Takashi Yamashita, Shinichi Sato, Yoshihide Asano, Chinnaswamy Tiruppathi, Anjana Yeldandi, Bettina C. Schock, Swati Bhattacharyya, John Varga
Summary: The reduced expression of A20 gene in systemic sclerosis (SSc) skin and lungs is associated with the development of fibrosis. The study suggests that A20 plays a critical role in restraining fibroblast activation and could be a potential target for fibrosis therapy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Olivier A. Pierrat, Manjuan Liu, Gavin W. Collie, Kartika Shetty, Matthew J. Rodrigues, Yann-Vai Le Bihan, Emma A. Gunnell, P. Craig McAndrew, Mark Stubbs, Martin G. Rowlands, Norhakim Yahya, Erald Shehu, Rachel Talbot, Lisa Pickard, Benjamin R. Bellenie, Kwai-Ming J. Cheung, Ludovic Drouin, Paolo Innocenti, Hannah Woodward, Owen A. Davis, Matthew G. Lloyd, Ana Varela, Rosemary Huckvale, Fabio Broccatelli, Michael Carter, David Galiwango, Angela Hayes, Florence Raynaud, Christopher Bryant, Steven Whittaker, Olivia W. Rossanese, Swen Hoelder, Rosemary Burke, Rob L. M. van Montfort
Summary: By recruiting corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls gene transcription required for B-cell germinal center formation. This study aims to discover small molecule inhibitors that disrupt BCL6-corepressor protein interaction, as BCL6 deregulation is implicated in Diffuse Large B-Cell Lymphoma development. The researchers used high throughput screening and various assays to identify hit series, determined X-ray structures of BCL6 bound to compounds, and developed biochemical and cellular assays to optimize compound potency.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Wenxia Wang, Swarna Bale, Bharath Yalavarthi, Priyanka Verma, Pei-Suen Tsou, Ken M. Calderone, Dibyendu Bhattacharyya, Gary J. Fisher, John Varga, Swati Bhattacharyya
Summary: RP105 has been identified as a novel cell-intrinsic negative regulator of TLR4-MD2-driven sustained fibroblast activation, and its impaired function may contribute to the progression of systemic sclerosis.
Article
Biochemistry & Molecular Biology
Shreosi Chatterjee, Abira Ganguly, Dibyendu Bhattacharyya
Summary: This study investigates nucleolar size reprogramming in Saccharomyces cerevisiae mutants with opposite effects on nucleolar size. Mutations in genes involved in nuclear functions cause enlargement of nuclei/nucleoli, while mutations in secretory pathway family genes lead to reduced nucleolar size. Moreover, the combination of nucleolar size-reducing mutations and specific mutants can effectively reprogram the nuclear/nucleolar size almost back to normal.
Article
Biochemistry & Molecular Biology
Daniel S. J. Miller, Sabine A. Voell, Izidor Sosic, Matic Proj, Olivia W. Rossanese, Gregor Schnakenburg, Michael Guetschow, Ian Collins, Christian Steinebach
Summary: A new generation of BRAF(V600E) degraders has been developed to avoid paradoxical activation of the MAPK pathway, providing a new approach for cancer therapy.
RSC MEDICINAL CHEMISTRY
(2022)