Article
Microbiology
Julianna Han, Ketaki Ganti, Veeresh Kumar Sali, Carly Twigg, Yifeng Zhang, Senthamizharasi Manivasagam, Chieh-Yu Liang, Olivia A. Vogel, Iris Huang, Shanan N. Emmanuel, Jesse Plung, Lillianna Radoshevich, Jasmine T. Perez, Anice C. Lowen, Balaji Manicassamy
Summary: It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion, but the exact role of host factors in genome assembly is not fully understood. This study shows that Rab11a+ vesicles play a crucial role in the congregation and assembly of vRNPs, enabling specific genome assembly and production of infectious virus particles. However, in the absence of Rab11a, viral RNA segments fail to congregate properly, resulting in defects in virus assembly and increased production of non-infectious particles.
Article
Multidisciplinary Sciences
Kohji Yamada, Saya Motohashi, Tsunekazu Oikawa, Naoko Tago, Rei Koizumi, Masaya Ono, Toshiaki Tachibana, Ayano Yoshida, Saishu Yoshida, Masayuki Shimoda, Masahiro Oka, Yoshihiro Yoneda, Kiyotsugu Yoshida
Summary: The study reveals the role of E-Syt1 in mediating cytosolic protein secretion at the ER-PM contact sites in liver cancer cells. SEC22B vesicles tethered to the PM via Q-SNAREs for their secretion, while PKC delta secretion and tumorigenicity were regulated by the interaction with E-Syt1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Dongmei Liu, Muriel Mari, Xia Li, Fulvio Reggiori, Susan Ferro-Novick, Peter Novick
Summary: This study discovered a process called ER-phagy, which selectively delivers fragments of the endoplasmic reticulum to the lysosome or vacuole in response to starvation or the accumulation of misfolded proteins. The loss of specific genes and proteins blocks the association between the autophagy receptor and the assembly scaffold protein, and a membrane contact site module is also found to be involved in ER-phagy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Sofia Dimou, Mariangela Dionysopoulou, Georgia Maria Sagia, George Diallinas
Summary: A study has found a non-conventional trafficking route that bypasses the Golgi for transporting nutrient transporters and other important membrane proteins to the fungal plasma membrane. This discovery expands the concept of Golgi-independent biogenesis and suggests that this could be a major and largely overlooked cargo-specific sorting route in eukaryotic cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Chung-Ling Lu, Steven Ortmeier, Jon Brudvig, Tamara Moretti, Jacob Cain, Simeon A. Boyadjiev, Jill M. Weimer, Jinoh Kim
Summary: SEC24 is crucial for cargo sorting during COPII vesicle assembly, with SEC24D mutations leading to osteogenesis imperfecta in humans. A study on mutant fish showed defects in collagen secretion, emphasizing the importance of SEC24D in this process. Procollagen export from the endoplasmic reticulum involves interactions with multiple SEC24 paralogs, with tissue-specific phenotypes resulting from their deficiency.
Review
Biochemistry & Molecular Biology
Ann Cuypers, Isabeau Vanbuel, Verena Iven, Kris Kunnen, Stephanie Vandionant, Michiel Huybrechts, Sophie Hendrix
Summary: Cadmium is a toxic compound that is harmful to human health and efforts are needed to remediate Cd-polluted soils. It is important to understand the molecular mechanisms underlying Cd stress responses in plants and develop strategies for economic validation of these soils.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Physiology
Vitalii Kryvenko, Istvan Vadasz
Summary: Protein transcription, translation, and folding are essential processes in living cells, with the endoplasmic reticulum (ER) playing a crucial role in these functions. Elevated CO2 levels can impair ER function, leading to both adaptive and maladaptive regulation of protein folding and maturation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Medicine, General & Internal
Na Li, Jinqiong Li, Jiantao Jia, Xia Yao, Yan Zhu
Summary: This study aims to investigate the relationship between miR-148a and preeclampsia (PE), and it was found that miR-148a regulates the endoplasmic reticulum stress (ERS) and apoptosis of placental cells by targeting the ERS protein X box binding protein 1 (XBP1). The experimental results showed that upregulation of miR-148a increased the levels of ERS and apoptosis in placental cells, while downregulation of miR-148a decreased these levels. Furthermore, it was found that the expression of XBP1 was significantly increased in PE patients compared to normal pregnant women.
Review
Biochemistry & Molecular Biology
Sanaz Dastghaib, P. Sravan Kumar, Sajjad Aftabi, Gautam Damera, Azadeh Dalvand, Adel Sepanjnia, Mohammad Kiumarsi, Mohamad-Reza Aghanoori, Sukhwinder Singh Sohal, Sudharsana R. Ande, Javad Alizadeh, Pooneh Mokarram, Saeid Ghavami, Pawan Sharma, Amir A. Zeki
Summary: Lung cells are exposed to internal and external stressors, leading to disruption of protein homeostasis and activation of the UPR. Dysregulation of the UPR is associated with disease development and various human conditions. Compounds targeting the UPR pathway show potential for future therapeutic interventions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Whendy Contreras, Caroline Wiesehofer, Dora Schreier, Nadja Leinung, Petra Peche, Gunther Wennemuth, Marc Gentzel, Bernd Schroder, Torben Mentrup
Summary: This study provides a detailed characterization of the C11orf94 protein, renamed as Frey, which plays a crucial role in the assembly of Izumo1 complexes. By retaining Izumo1 in the endoplasmic reticulum, Frey facilitates its incorporation into high molecular weight complexes.
Article
Multidisciplinary Sciences
Giorgia Di Lorenzo, Francescopaolo Iavarone, Marianna Maddaluno, Ana Belen Plata-Gomez, Simone Aureli, Camila Paz Quezada Meza, Laura Cinque, Alessandro Palma, Alessio Reggio, Carmine Cirillo, Francesca Sacco, Alexandra Stolz, Gennaro Napolitano, Oriano Marin, Lorenzo A. Pinna, Maria Ruzzene, Vittorio Limongelli, Alejo Efeyan, Paolo Grumati, Carmine Settembre
Summary: Selective degradation of the endoplasmic reticulum (ER) via autophagy is initiated by ER-phagy receptors, such as FAM134C, which is activated by phosphorylation by CK2 during starvation. This study also reveals the regulatory role of mTORC1 in FAM134C phosphorylation.
Review
Biology
Hidekatsu Yanai, Hiroki Adachi, Mariko Hakoshima, Hisayuki Katsuyama
Summary: Mitochondria are organelles that generate adenosine triphosphate through aerobic respiration. Imeglimin is a novel oral hypoglycemic agent that targets mitochondrial function and reduces reactive oxygen species production. It improves glucose metabolism, preserves pancreatic beta-cell mass, inhibits hepatic glucose production, and improves insulin sensitivity. Imeglimin also improves vascular dysfunction and reduces ischemia-induced brain damage. It can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.
Article
Immunology
Wei Wang, Xiaodan Qin, Liang Lin, Jia Wu, Xiuyuan Sun, Ye Zhao, Yurong Ju, Ziheng Zhao, Liwei Ren, Xuewen Pang, Youfei Guan, Yu Zhang
Summary: This study reveals the crucial role of PGE(2)-EP4 signaling in humoral immunity, which controls the life span of plasma cells by activating AKT to regulate the activation of IRE1α and maintain endoplasmic reticulum homeostasis.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Wei Wang, Xiaodan Qin, Liang Lin, Jia Wu, Xiuyuan Sun, Ye Zhao, Yurong Ju, Ziheng Zhao, Liwei Ren, Xuewen Pang, Youfei Guan, Yu Zhang
Summary: The study demonstrates the highly selective impact of the PGE(2)-EP4 signal on humoral immunity, and provides a link between ER stress response and the life span of SLPCs.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Environmental Sciences
Senlin Li, Renjie Wang, Zhaolai Dai, Chao Wang, Zhenlong Wu
Summary: The study found that adding Yucca schidigera extract significantly alleviated the growth arrest, intestinal dysfunction, and oxidative damage caused by heat stress in tilapia. This effect may be related to the regulation of the ubiquitin-proteasome system and inflammatory factors by Yucca supplementation.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemical Research Methods
Soumya Mukherjee, Andris Jankevics, Florian Busch, Markus Lubeck, Yang Zou, Gary Kruppa, Albert J. R. Heck, Richard A. Scheltema, Karli R. Reiding
Summary: Ion mobility enables spatial separation of ions in the gas phase, providing information about their size. The timsTOF Pro device can physically separate N-glycopeptides from nonmodified peptides and produce high-quality fragmentation spectra. This method allows for the effective selection of analytes of interest based on the clear cluster in the mobiologram formed by the glycan moieties enlarging the size of glycopeptides.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Chemistry, Multidisciplinary
Evolene Desligniere, Amber Rolland, Eduard H. T. M. Ebberink, Victor Yin, Albert J. R. Heck
Summary: Native mass spectrometry is widely used for determining the mass of intact proteins and their biomolecular assemblies. However, it can be challenging for heterogeneous protein complexes. In 2012, an Orbitrap-based mass analyzer with extended mass range was introduced, enabling high-resolution mass spectra of large protein assemblies and single ion measurements. This led to the development of single-molecule Orbitrap-based charge detection mass spectrometry in 2020, which has opened doors for innovative research in various systems.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C. Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J. R. Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
Summary: In this study, previously unrecognized cAMP nanodomains associated with beta-adrenergic stimulation were identified using an integrated phosphoproteomics approach and network analysis. The composition and function of one of these nanodomains were validated. The findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors.
CIRCULATION RESEARCH
(2023)
Article
Biochemical Research Methods
Shelley Jager, Dario A. T. Cramer, Albert J. R. Heck
Summary: Alpha-1-antitrypsin (A1AT) has been suggested as a potential biomarker for distinguishing healthy and diseased individuals. However, the variability of the SERPINA1 gene in the general population may affect A1AT expression and serum protein levels, which are often overlooked in proteomics studies. This study found significant differences in allele-specific protein serum levels of A1AT among heterozygous donors, suggesting the importance of considering these factors when analyzing A1AT as a potential serum biomarker.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Andrology
Min Zhang, Riccardo Zenezini Chiozzi, Elizabeth G. Bromfield, Albert J. R. Heck, J. Bernd Helms, Bart M. Gadella
Summary: This study aimed to identify the interacting partners of CRISP2. The interactions of these binding partners were investigated under different conditions. The results suggest that CRISP2 may act as a scaffold for protein complex formation and dissociation to ensure the correct positioning of proteins required for the acrosome reaction and zona pellucida penetration.
Article
Biology
Leire Aguinagalde Salazar, Maurits A. den Boer, Suzanne M. Castenmiller, Seline A. Zwarthoff, Carla de Haas, Piet C. Aerts, Frank J. Beurskens, Janine Schuurman, Albert J. R. Heck, Kok van Kessel, Suzan H. M. Rooijakkers
Summary: In this study, it is found that by modifying the structure of monoclonal antibodies (mAbs), the immune protection and bactericidal effect against Streptococcus pneumoniae can be improved. The modified mAbs effectively activate the complement system and recruit complement component C1 for bacterial clearance, enhancing the antibacterial activity against various serotypes of pneumococci. This study provides an important proof of concept for the future development of antibody therapies against encapsulated bacteria.
Article
Biotechnology & Applied Microbiology
Yen-Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song, Ulla Mandel, Claus Kristensen, Lorenzo Povolo, Andre R. A. Marques, Tomislav Caval, Albert J. R. Heck, Julio Lopes Sampaio, Ludger Johannes, Takahiro Tsukimura, Robert Desnick, Sergey Y. Y. Vakhrushev, Zhang Yang, Henrik Clausen
Summary: Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due to short circulation times and suboptimal biodistribution of the therapeutic enzymes. Researchers have engineered Chinese hamster ovary (CHO) cells to produce glycoengineered enzymes, which have improved circulation time and biodistribution. This glycoengineering approach, known as Long-Acting-GlycoDesign (LAGD), may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Cell Biology
Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinie, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J. R. Heck, Judy Hirst, Nils-Goran Larsson
Summary: The mammalian respiratory chain complexes CI, CIII2, and CIV form a stable assembly called the respirasome, which is critical for cellular bioenergetics. By studying knockin mice with decreased levels of respirasomes, researchers found that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice. However, the alternate functions of respirasomes, such as regulating protein stability and preventing age-associated protein aggregation, need further investigation.
Article
Biochemistry & Molecular Biology
Yetao Wang, Lawrence Lifshitz, Noah J. Silverstein, Esther Mintzer, Kevin Luk, Pamela StLouis, Michael A. Brehm, Scot A. Wolfe, Steven G. Deeks, Jeremy Luban
Summary: Innate lymphoid cells (ILCs) are a diverse population of cells that include NK cells and play important roles in tissue homeostasis and repair, inflammation, and protection from infection. This study used transcriptional and chromatin profiling to investigate the interplay between human blood ILCs and their responses to HIV-1 infection. The findings reveal the existence of four main ILC subsets in human blood and provide insights into how HIV-1 infection disrupts NK cells and their homeostatic function.
Article
Multidisciplinary Sciences
Guangai Xue, Hyun Jae Yu, Cindy Buffone, Szu-Wei Huang, KyeongEun Lee, Shih Lin Goh, Anna T. T. Gres, Mehmet Hakan Guney, Stefan G. G. Sarafianos, Jeremy Luban, Felipe Diaz-Griffero, Vineet N. N. KewalRamani
Summary: The entry of HIV-1 into the nucleus is regulated by the interaction between the viral capsid protein CA and nuclear pore complex proteins Nup35 and POM121. This interaction is also influenced by soluble host factors such as Cyclophilin A. These findings highlight the role of CA as a macromolecular nuclear transport receptor and provide insights into the mechanism of HIV-1 nuclear invasion.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Inge Gazi, Karli R. Reiding, Andre Groeneveld, Jan Bastiaans, Thom Huppertz, Albert J. R. Heck
Summary: We monitored the changes in bovine milk IgG over a 28-day period after calving, finding that IgG accounts for over 50% of protein content in colostrum but less than 3% in mature milk. The N-glycosylation profile of bovine milk IgG was found to be highly heterogeneous with over 40 glycoforms, and this profile changed significantly during lactation. We also identified the presence of IgG3 subtype in bovine milk, alongside IgG1 and IgG2. These findings are important for understanding calf's immune development and the nutritional value of bovine milk.
Article
Immunology
Kelly A. Dingess, Max Hoek, Danique M. H. van Rijswijk, Sem Tamara, Maurits A. den Boer, Tim Veth, Mirjam J. A. Damen, Arjan Barendregt, Michelle Romijn, Hannah G. Juncker, Britt J. van Keulen, Gestur Vidarsson, Johannes B. van Goudoever, Albert Bondt, Albert J. R. Heck
Summary: The most abundant immunoglobulin in the human body is IgA and it is found in high concentrations in mucosal lining and biofluids like milk. The structure and clonal repertoire of IgA1-containing molecular assemblies were analyzed using mass spectrometry-based approach in serum and milk from three donors. The results showed that serum IgA1 consists of two distinct structural populations, monomeric IgA1 and dimeric J-chain coupled IgA1, while IgA1 in milk is present only as secretory IgA (SIgA) with various assemblies. The IgA1-Fab repertoires in serum and milk were also found to be different.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)