Article
Biochemistry & Molecular Biology
Jia-Jin Liu, Po-Huang Liang
Summary: This study investigates the differences in dolichol synthesis between plants and animals by studying the homologues of dehydrodolichyl diphosphate synthases (DHDDSs) and cis-prenyltransferases (cis-PTs) in Cinnamomum kanehirae. The researchers discovered that plants have multiple cis-PT homologues, which can either pair or stand alone to produce different chain-length products. Additionally, the study reveals the possible evolutionary paths of these proteins based on their roles in polyprenol and dolichol biosynthesis and sequence motifs.
Article
Chemistry, Organic
Mario M. de Capitani, Ana S. Ramirez, Lorenzo Rossi, J. Andrew N. Alexander, Sabrina De Lorenzo, Kaspar P. Locher, Jean-Louis Reymond
Summary: We report the synthesis of two fluorescently labelled analogues of C25 dolichol (Dol25), which can be accepted by eukaryotic protein N-glycosylation enzymes. The fluorescent labels facilitate handling and purification of the lipid-linked glycosyl donors and acceptors, and should facilitate further biochemical studies of protein glycosylation enzymes.
Article
Microbiology
Zlata Vershinin, Marianna Zaretsky, Ziqiang Guan, Jerry Eichler
Summary: The study identified three novel glycosyltransferases in the N-glycosylation pathway of Halobacterium salinarum and demonstrated the impacts of compromised N-glycosylation on various aspects of cell behavior, including protein modification and gene transcription.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Analytical
James W. Dressman, Colin T. McDowell, Xiaowei Lu, Peggi M. Angel, Richard R. Drake, Anand S. Mehta
Summary: N-linked glycosylation plays a crucial role in immune response and cell-to-cell interactions. The current analytical techniques for studying immune cell N-glycosylation have limitations in throughput, structural information, starting materials, and cell purification. This study proposes a rapid antibody array-based approach coupled with MALDI-IMS for analyzing cellular N-glycosylation, which provides a valuable tool for glycoimmunology research and clinical applications.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zlata Vershinin, Marianna Zaretsky, Ziqiang Guan, Jerry Eichler
Summary: This study reexamined the composition of N-linked glycans in Halobacterium salinarum, revealing a tetrasaccharide composition. Additionally, the absence of oligosaccharyltransferase AglB led to the accumulation of methylated and disulfated tetrasaccharides linked to dolichol phosphate. These findings contribute to a better understanding of the N-glycosylation pathway in this organism.
Article
Biochemical Research Methods
Xiaoyang Hou, Yu Wang, Dongbo Bu, Yaojun Wang, Shiwei Sun
Summary: N-linked glycosylation is a crucial protein modification involved in various biological processes. The EMNGly approach, which combines machine learning and deep learning, improves glycosylation site prediction accuracy and outperforms existing techniques.
Article
Chemistry, Analytical
Miloslav Sanda, Lindsay Morrison, Radoslav Goldman
Summary: The outbreak of the Covid-19 pandemic has caused the current global health crisis, prompting the need for detailed studies on SARS-CoV-2 proteins to develop effective antiviral compounds and vaccines. The glycosylation of the spike (S) protein plays a significant role in its proteolytic activation, expanding the current knowledge in this area.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Matheus A. Meirelles, Jean-Louis Reymond
Summary: This study presents an optimized synthesis method for a probe used in studying protein N-glycosylation in eukaryotic cells. The yields and reaction times of three phosphate coupling steps were improved by adjusting reagents and conditions. An efficient purification protocol was also developed to obtain the pure product.
HELVETICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Yevgen Zolotarov, Chao Ma, Irene Gonzalez-Recio, Serge Hardy, Gijs A. C. Franken, Noriko Uetani, Femke Latta, Elie Kostantin, Jonathan Boulais, Marie-Pier Thibault, Jean-Francois Cote, Irene Diaz Moreno, Antonio Diaz Quintana, Joost G. J. Hoenderop, Luis Alfonso Martinez-Cruz, Michel L. Tremblay, Jeroen H. F. de Baaij
Summary: In this study, ARL15 was identified as a novel negative regulator of Mg2+ transport by promoting the complex N-glycosylation of CNNMs. The interaction between ARL15 and CNNM family members was found to be important for cellular localization in the kidney. Knockdown of ARL15 resulted in a significant increase in Mg-25(2+) uptake in multiple kidney cancer cell lines.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Organic
Dancan K. Njeri, Erik Alvarez Valenzuela, Justin R. Ragains
Summary: By substituting the benzyl groups of glucosyl imidate donors with trifluoromethyl, a substantial increase in 1,2-cis-selectivity can be achieved when activated with TMS-I in the presence of triphenylphosphine oxide. The stereoselectivity depends on the number of trifluoromethyl groups, leading to high 1,2-cis-selectivity with reactive alcohol acceptors.
Review
Chemistry, Multidisciplinary
Akihiro Ishiwata, Katsunori Tanaka, Jiaming Ao, Feiqing Ding, Yukishige Ito
Summary: 1,2-cis-O-glycosylation is essential in the assembly of bioactive glycans with various functions. However, controlling the stereoselectivity of glycosylation and specifically forming 1,2-cis glycosides is challenging. Recent advances in glycosyl donor modification, reaction conditions, and activation methods have been made in the development of 1,2-cis selective glycosylations.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Xianglai Liu, Yingying Song, Ao Liu, Yueer Zhou, Qian Zhu, Yetong Lin, Huiyong Sun, Kaidi Zhu, Wei Liu, Ning Ding, Weijia Xie, Haopeng Sun, Biao Yu, Peng Xu, Wei Li
Summary: The study demonstrates that PTFAI can serve as a stereodirecting group for 1,2-cis alpha-glycosylation, leading to improved selectivity in glycosylation reactions. The involvement of 6-PTFAI in remote participation was confirmed using low-temperature NMR, shedding light on the reaction mechanism. This strategy shows promise for the synthesis of complex carbohydrates and derivatives.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Applied
Zuzana Meszaros, Lucie Petraskova, Natalia Kulik, Helena Pelantova, Pavla Bojarova, Vladimir Kren, Kristyna Slamova
Summary: Fungal beta-N-acetylhexosaminidases are important tools for the synthesis of natural and modified oligosaccharides and glycoconjugates. In this study, the enzyme from Aspergillus oryzae was engineered to shift its reaction from hydrolysis to transglycosylation. Nine mutant variants of the enzyme were designed and tested, and one variant (V306W/Y445N AoHex) showed superior transglycosidase activity with a transglycosylation-to-hydrolysis ratio greater than 110, which is unique among similar mutants.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Plant Sciences
Richard Strasser, Georg Seifert, Monika S. Doblin, Kim L. Johnson, Colin Ruprecht, Fabian Pfrengle, Antony Bacic, Jose M. Estevez
Summary: Glycosylation is a crucial modification process that can alter the biological function of proteins and lipids, affecting the development and physiology of an organism. While challenges remain in understanding plant glycosylation, high throughput approaches may help to address these gaps, revolutionizing the identification and characterization of unknown plant glycosyltransferases and hydrolases.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemical Research Methods
Jennyfer Tena, Izumi Maezawa, Mariana Barboza, Maurice Wong, Chenghao Zhu, Michael Russelle Alvarez, Lee-Way Jin, Angela M. Zivkovic, Carlito B. Lebrilla
Summary: The proteins in the cell membrane of the brain are modified by glycans, and these modifications play a crucial role in cell-cell interactions. This study analyzed the N-glycome and N-glycoproteome of the brain in different regions, and discovered regional variations in glycan types. Furthermore, differences in the glycomic and glycoproteomic profiles were observed between individuals with Alzheimer's disease, hippocampal sclerosis, and no cognitive impairment.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Multidisciplinary Sciences
Victor Garcia, Eon Joo Park, Mauro Siragusa, Florian Frohlich, Mohammad Mahfuzul Haque, Jonathan V. Pascale, Katherine R. Heberlein, Brant E. Isakson, Dennis J. Stuehr, William C. Sessa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Hematology
Xinbo Zhang, Cristina M. Ramirez, Binod Aryal, Julio Madrigal-Matute, Xinran Liu, Antonio Diaz, Marta Torrecilla-Parra, Yajaira Suarez, Ana M. Cuervo, William C. Sessa, Carlos Fernandez-Hernando
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2020)
Editorial Material
Cell Biology
Nabil E. Boutagy, Joseph W. Fowler, William C. Sessa
Article
Gastroenterology & Hepatology
Yilin Yang, Panjamaporn Sangwung, Reiichiro Kondo, Yirang Jung, Matthew J. McConnell, Jain Jeong, Teruo Utsumi, William C. Sessa, Yasuko Iwakiri
Summary: The study demonstrates that liver sinusoidal endothelial cells can metabolize alcohol, revealing the mechanism of alcohol-induced LSEC dysfunction and liver injury. A potential therapeutic strategy involves blocking acetylation of Hsp90 specifically in LSECs via adeno-associated virus-mediated gene delivery to ameliorate alcohol-induced liver injury.
JOURNAL OF HEPATOLOGY
(2021)
Article
Genetics & Heredity
Carolina Courage, Karen L. Oliver, Eon Joo Park, Jillian M. Cameron, Kariona A. Grabinska, Mikko Muona, Laura Canafoglia, Antonio Gambardella, Edith Said, Zaid Afawi, Betul Baykan, Christian Brandt, Carlo di Bonaventura, Hui Bein Chew, Chiara Criscuolo, Leanne M. Dibbens, Barbara Castellotti, Patrizia Riguzzi, Angelo Labate, Alessandro Filla, Anna T. Giallonardo, Geza Berecki, Christopher B. Jackson, Tarja Joensuu, John A. Damiano, Sara Kivity, Amos Korczyn, Aarno Palotie, Pasquale Striano, Davide Uccellini, Loretta Giuliano, Eva Andermann, Ingrid E. Scheffer, Roberto Michelucci, Melanie Bahlo, Silvana Franceschetti, William C. Sessa, Samuel F. Berkovic, Anna-Elina Lehesjoki
Summary: Progressive myoclonus epilepsies (PMEs) are a group of clinically and genetically heterogeneous rare diseases, with over 70% of cases now molecularly solved. By performing whole-exome sequencing on unsolved PME-affected individuals, novel disease-causing variants were identified, particularly in cases studied with additional family members. A variety of new genes related to lysosomal and endosomal function were discovered, shedding light on the genetic complexity of PME.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biology
Takeshi Ninchoji, Dominic T. Love, Ross O. Smith, Marie Hedlund, Dietmar Vestweber, William C. Sessa, Lena Claesson-Welsh
Summary: In this study, suppression of nitric oxide formation resulted in reduced retinal neoangiogenesis and decreased vascular leakage through stabilized endothelial adherens junctions. This has important implications for preventing vascular leakage in ocular diseases.
Article
Ophthalmology
Pascal N. Bernatchez, Bo Tao, Ralph A. Bradshaw, David Eveleth, William C. Sessa
Summary: The study aimed to identify a novel CPP for improved delivery of a truncated Cav modulator. Results showed that fusion with peptide RRPPR efficiently blocked NO release and VEGF-induced permeability, reducing immune-mediated retinal damage.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Hyojin Park, Jessica Furtado, Mathilde Poulet, Minhwan Chung, Sanguk Yun, Sungwoon Lee, William C. Sessa, Claudio A. Franco, Martin A. Schwartz, Anne Eichmann
Summary: This study demonstrates the critical role of ALK1 in controlling endothelial cell polarization against blood flow direction and promoting vein-to-artery migration, while identifying integrin-YAP/TAZ signaling blockers as potential targets for preventing vascular malformations in patients with hereditary hemorrhagic telangiectasia.
Article
Biology
Joseph Wayne M. Fowler, Rong Zhang, Bo Tao, Nabil E. Boutagy, William C. Sessa
Summary: The relationship between cholesterol homeostasis and immunity in leukocytes has been extensively studied, but not much is known about this relationship in vascular endothelium cells. This study reveals the role of cholesterol and the transcription regulator SREBP2 in the inflammatory response of endothelial cells.
Article
Biochemistry & Molecular Biology
Joseph Wayne M. Fowler, Nabil E. Boutagy, Rong Zhang, Daiki Horikami, Michael B. Whalen, Casey E. Romanoski, William C. Sessa
Summary: The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and has been implicated in leukocyte immune responses. In this study, the role of SREBP2 in endothelial cells was investigated, revealing its impact on inflammatory chemokine production and interferon response genes.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Wenping Zhou, Wenxue Li, Shisheng Wang, Barbora Salovska, Zhenyi Hu, Bo Tao, Yi Di, Ujwal Punyamurtula, Benjamin E. E. Turk, William C. C. Sessa, Yansheng Liu
Summary: The authors used optogenetics and mass spectrometry-based phosphoproteomics to study the effects of different intensities, durations, and patterns of Akt1 activation on phosphorylation circuits, revealing downstream signaling outcomes of Akt1. The study showed that different intensities, durations, and patterns of Akt1 activation lead to distinct phosphorylation profiles in vascular endothelial cells, and also revealed the interaction between Akt1 signaling and growth factor signaling in these cells. The resulting dataset provides an important resource for future studies on AKT signaling and dynamics.
NATURE COMMUNICATIONS
(2023)
Review
Gastroenterology & Hepatology
Michele A. Rodrigues, Dawidson A. Gomes, Romina Fiorotto, Mateus T. Guerra, Jittima Weerachayaphorn, Tao Bo, William C. Sessa, Mario Strazzabosco, Michael H. Nathanson
Summary: Fluid and bicarbonate secretion in cholangiocytes is regulated by ITPR3, which localizes to the apical region. This localization is dependent on intact lipid rafts and interactions with CAV1 and MYH9. Disruption of lipid rafts or knockdown of CAV1 or MYH9 impairs ITPR3 localization and secretion.
HEPATOLOGY COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Nabil E. Boutagy, Abhishek K. Singh, William C. Sessa
Summary: Obesity is a major contributor to insulin resistance and type 2 diabetes, increasing the risk of cardiovascular disease. Metabolic changes caused by obesity negatively affect the vasculature, exacerbating disease progression. Understanding the cellular and molecular processes is crucial for optimizing medical therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Ainara G. Cabodevilla, Songtao Tang, Sungwoon Lee, Adam E. Mullick, Jose O. Aleman, M. Mahmood Hussain, William C. Sessa, Nada A. Abumrad, Ira J. Goldberg
Summary: Despite the primary role of LpL in tissue uptake of fatty acids from chylomicrons, studies have shown that an additional pathway exists for transferring dietary lipids to tissues. This pathway involves endothelial cell uptake of chylomicrons, hydrolysis in lysosomes, and subsequent lipid accumulation in cells. Competing with HDL and targeting the scavenger receptor-BI can inhibit this process in vivo, potentially reducing lipid accumulation in tissues and preventing conditions such as eruptive xanthomas.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
Qianying Yuan, Abdul Basit, Wenhua Liang, Rihao Qu, Yi Luan, Chunguang Ren, Ao Li, Xin Xu, Xiaoqing Liu, Chun Yang, Andrew Kuo, Richard Pierce, Longbo Zhang, Benjamin Turk, Xin Hu, Fangyong Li, Weixue Cui, Run Li, Danxia Huang, Lili Mo, William C. Sessa, Patty J. Lee, Yuval Kluger, Bing Su, Wenwen Tang, Jianxing He, Dianqing Wu
Summary: Pazopanib ameliorates ALI manifestations by inhibiting the phosphorylation of NADPH oxidase 2 subunit p47(phox) through MAP3K2 and MAP3K3. This drug also reduces edema in human lung transplantation recipients, indicating potential for treating ALI.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
