Article
Multidisciplinary Sciences
Bjoern U. Klink, Eric Herrmann, Claudia Antoni, Lars Langemeyer, Stephan Kiontke, Christos Gatsogiannis, Christian Ungermann, Stefan Raunser, Daniel Kuemmel
Summary: This study presents a high-resolution cryogenic electron microscopy structure of the Mon1-Ccz1 complex, revealing its strong scaffold for the catalytic center and the phosphatidylinositol phosphate-binding site, providing molecular insights into endosomal Rab activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Qingchun Lu, Po-Shun Wang, Ling Yang
Summary: This review focuses on highlighting Golgi-associated Rab GTPases as master regulators of autophagic flux, discussing the future research prospects in elucidating their role and mechanism in autophagy and autophagy-related diseases.
CELL AND BIOSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Antonio Galindo, Sean Munro
Summary: Transport Protein Particle (TRAPP) complexes are conserved complexes that act as nucleotide exchange factors for Rab GTPases. They play roles in protein secretion, autophagy, and other processes. There are two complexes in metazoans: TRAPPII activates Rab11, and TRAPPIII activates Rab1. Crystal and cryo-EM structures have provided insights into the organization and activation mechanisms of these complexes.
Article
Multidisciplinary Sciences
Alison Boutet, Carlos Zeledon, Gregory Emery
Summary: Chemotaxis is important for diverse migrations in development and diseases like cancer progression. In this study, the researchers investigated the role of ArfGAP1 in regulating chemotaxis during collective cell migration. They found that ArfGAP1 is required to maintain receptor tyrosine kinases at the plasma membrane, and its absence leads to decreased active receptors and increased late endosomes. They also observed increased late endosomes and lysosomes in the absence of ArfGAP1, and identified genetic interactions with Lrrk in receptor sorting.
Article
Biochemistry & Molecular Biology
Rosanne Persaud, Sheena C. Li, Joseph D. Chao, Roberto Forestieri, Elizabeth Donohue, Aruna D. Balgi, Xingji Zheng, Jesse T. Chao, Yoko Yashiroda, Mami Yoshimura, Christopher J. R. Loewen, Anne-Claude Gingras, Charles Boone, Yossef Av-Gay, Michel Roberge, Raymond J. Andersen
Summary: A study found that the marine natural product clionamines can activate autophagy and inhibit the survival of Mycobacterium tuberculosis in macrophages. Pik1 was identified as the target protein of clionamines using a yeast chemical-genetics approach. Further research revealed that PI4KB is an unexploited molecular target that, when knocked down, can inhibit the survival of Mycobacterium tuberculosis in macrophages.
CELL CHEMICAL BIOLOGY
(2022)
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)
Review
Plant Sciences
Yutaro Shimizu, Tomohiro Uemura
Summary: Membrane trafficking is crucial for organelle maintenance and function, and the TGN plays a critical role as a sorting station. Recent studies have identified distinct subdomains of the TGN for different trafficking pathways.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Cell Biology
Azumi Yoshimura, Stephanie Miserey-Lenkei, Evelyne Coudrier, Bruno Goud
Summary: Arp2/3 inhibition affects the acetylated microtubule network and induces abnormal accumulation of long RAB1/GM130-positive carriers, resulting in a decreased rate of anterograde cargo arrival at the Golgi apparatus.
Review
Biochemistry & Molecular Biology
Alazne Arrazola Sastre, Miriam Luque Montoro, Hadriano M. Lacerda, Francisco Llavero, Jose L. Zugaza
Summary: Rab and Arf GTPases play crucial roles in the pathogenesis and progression of neurodegenerative diseases, making them potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Ida Marie Modvig, Rune Ehrenreich Kuhre, Sara Lind Jepsen, Stella Feng Sheng Xu, Maja Storm Engelstoft, Kristoffer Lihme Egerod, Thue Walther Schwartz, Cathrine Orskov, Mette Marie Rosenkilde, Jens Juul Holst
Summary: This study aimed to explore individual amino acid-stimulated GLP-1 responses and the underlying mechanisms, as well as to identify the amino acid-sensing receptors involved in amino acid-stimulated GLP-1 release. Using isolated perfused rat small intestines, the research found that amino acids differ in their capacity to stimulate GLP-1 secretion and that CaSR plays a crucial role in sensing absorbed amino acids for GLP-1 release.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Cell Biology
Kana Fujibayashi, Joji Mima
Summary: Arf-family small GTPases play crucial roles in membrane trafficking and tethering processes. Arf6 can act as a membrane tether by physically linking distinct lipid bilayers, while Arf1 exhibits weaker membrane tethering capability under current experimental conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Oliver B. Davis, Hijai R. Shin, Chun-Yan Lim, Emma Y. Wu, Matthew Kukurugya, Claire F. Maher, Rushika M. Perera, M. Paulina Ordonez, Roberto Zoncu
Summary: Lysosomes play a crucial role in maintaining cellular homeostasis through macromolecular hydrolysis and metabolic signaling. In Niemann-Pick type C (NPC), abnormal cholesterol accumulation in lysosomes causes mTORC1 hyperactivation, leading to mitochondrial dysfunction and neurodegeneration. Proteomic profiling of NPC lysosomes reveals impaired proteolysis, hydrolase depletion, membrane damage, and defective mitophagy, highlighting the role of aberrant cholesterol-mTORC1 signaling in organelle pathogenesis.
DEVELOPMENTAL CELL
(2021)
Article
Multidisciplinary Sciences
Amulya Priya, Sandra Antoine-Bally, Anne-Sophie Mace, Pedro Monteiro, Valentin Sabatet, David Remy, Florent Dingli, Damarys Loew, Constantinos Demetriades, Alexis M. Gautreau, Philippe Chavrier
Summary: This study reveals an unprecedented interplay between actin and mTORC1 signaling on the endolysosomal system. Actin is required for proper association of RAGC and mTOR with endolysosomes, and perturbation of RAGC function affects the size of endolysosomal actin, suggesting a regulation of actin filament capping by RAGC.
Article
Cell Biology
Makoto Nagano, Kaito Aoshima, Hiroki Shimamura, Daria Elisabeth Siekhaus, Junko Y. Toshima, Jiro Toshima
Summary: Clathrin-mediated vesicle trafficking is essential for post-Golgi transport. The AP-1 complex and GGA adaptors in yeast are involved in the generation of distinct transport vesicles at the trans-Golgi network (TGN), while Ent3p/5p act as accessories for these adaptors. Our study reveals the importance of TGN vesicle transport in yeast Rab5-mediated endosome formation, with Ent3p/5p playing a crucial role in this process, while AP-1 and GGA adaptors are dispensable. Furthermore, we demonstrate the functional relationships between clathrin adaptors in the regulation of Vps21p activity in the TGN-endosome trafficking pathway.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Timothy J. Fazekas, Jill W. Alty, Eliza K. Neidhart, Austin S. Miller, Frank A. Leibfarth, Erik J. Alexanian
Summary: This study reports an approach to achieve diverse functionality on hydrocarbons by utilizing radical chain transfer. By using an easily prepared reagent, a range of functionalizations on small molecules and polyolefins can be achieved. This method has also been applied in the processing of plastic waste and enables the introduction of ionic functionality on polyolefins, transforming them into elastomers with high-value properties.
Article
Biochemical Research Methods
Siu Kwan Sze, Gnanasekaran JebaMercy, SoFong Cam Ngan
Summary: Deamidation is a degenerative protein modification that disrupts protein structure and function, playing a critical role in human aging and degenerative diseases. However, the study of deamidation has been limited by technical challenges in complex biological samples. New technologies, such as mixed mode electrostatic-interaction modified hydrophilic interaction liquid chromatography (emHILIC), are being developed to overcome these challenges and accurately analyze protein deamidation in complex samples.
Article
Cell Biology
Xiuping Sun, Divyanshu Mahajan, Bing Chen, Zhiwei Song, Lei Lu
Summary: The mechanism of Golgi localization of Golgi glycosyltransferases has been found to be primarily through retention rather than retrieval. The study also revealed the contributions of different regions of ST6GAL1 to Golgi retention, showing that the N-terminal cytosolic tail and transmembrane domain can act as Golgi export signals.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Hieng Chiong Tie, Divyanshu Mahajan, Lei Lu
Summary: We have developed a new method to visualize the organization and intra-Golgi transport of proteins at the cisternal level using light microscopy. By analyzing side-view images of more than 30 Golgi proteins, we uncovered the spatial organization of different regions within the Golgi and observed the transport of cargo from one side to the other.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Uthra Balasubramaniyan Iyer, Jung Eun Park, Siu Kwan Sze, Zbynek Bozdech, Mark Featherstone
Summary: This study provides physical evidence for the presence of the Mediator complex in Plasmodium falciparum and identifies several interaction partners that play important roles in gene expression and mRNA processing. The study also suggests a possible crosstalk between endoplasmic reticulum function and the transcriptional machinery.
Article
Biology
Meng Shi, Hieng Chiong Tie, Mahajan Divyanshu, Xiuping Sun, Yan Zhou, Boon Kim Boh, Leah A. Vardy, Lei Lu
Summary: This study reveals the binding of Arl15 to Smad4 and its role in promoting the assembly of the Smad complex. Furthermore, Arl15 positively regulates TGF-β family signaling.
Article
Cell Biology
Juliane O. Viegas, Gajendra Kumar Azad, Yuan Lv, Lior Fishman, Tal Paltiel, Sundararaghavan Pattabiraman, Jung Eun Park, Daniel Kaganovich, Siu Kwan Sze, Michal Rabani, Miguel A. Esteban, Eran Meshorer
Summary: CAPRIN1 is a factor that regulates an RNA degradation pathway in embryonic stem cells, and it has significant effects on early differentiation and gene expression programs.
DEVELOPMENTAL CELL
(2022)
Article
Biochemistry & Molecular Biology
Divyanshu Mahajan, Viswanadh Madugula, Lei Lu
Summary: Ar1l3b, an ARF/Arl-family GTPase, is crucial for ciliary organization, trafficking, and signaling. Rab8-GDP and TNPO1 directly bind to the C-terminal stretch of Ar1l3b containing the RVEP motif, and Rab8-GDP enhances the interaction between TNPO1 and Ar1l3b. Mutation of the RVEP motif abolishes the interaction between the C-terminal stretch and Rab8-GDP/TNPO1. Knock-down of Rab8 or TNPO1 decreases the ciliary localization of Ar1l3b.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Bamaprasad Dutta, Shining Loo, Antony Kam, Siu Kwan Sze, James P. Tam
Summary: Hypoxia-induced vascular endothelial dysfunction (VED) is a significant contributor to severe human diseases. The discovery of ginsentide TP1, a microprotein in ginseng, has shown promising results in reducing vascular dysfunction. This study identifies new proteins synthesized in hypoxia and demonstrates the protective effects of ginsentide TP1 against hypoxia and ER stress in human endothelial cells.
Article
Cell Biology
Jose Antonio Sanchez Milan, Maria Fernandez-Rhodes, Xue Guo, Maria Mulet, SoFong Cam Ngan, Ranjith Iyappan, Maryam Katoueezadeh, Siu Kwan Sze, Aida Serra, Xavier Gallart-Palau
Summary: This study provides a comprehensive analysis of the impact of oxidative stress and phosphorylation on the aging process. The results show that trioxidized cysteine residues accumulate in the aging proteome and interact with enzymes involved in phosphorylation signaling, altering their structures in a similar way to phosphorylated serine residues. These findings are significant for understanding the interplay between oxidative stress and phosphorylation in aging, and open new avenues for research on protein modifications in chronic diseases and aging.
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
Multidisciplinary Sciences
Tomoki Naito, Haoning Yang, Dylan Hong Zheng Koh, Divyanshu Mahajan, Lei Lu, Yasunori Saheki
Summary: Abnormal distribution of cellular cholesterol is associated with various diseases, and maintaining its proper distribution is crucial for cellular homeostasis. This study uncovers the important role of lipid transfer proteins ORP9, OSBP, and GRAMD1s in regulating cholesterol levels in the Golgi and plasma membrane.
NATURE COMMUNICATIONS
(2023)