Article
Biochemistry & Molecular Biology
Yongtian Chen, Jing Kang, Ru Zhen, Liyang Zhang, Caiyong Chen
Summary: Vesicle trafficking is a critical cellular process in eukaryotes, and this study identifies CCT4 as a key regulator of protein secretion and vesicle trafficking. The deficiency of CCT4 impairs the trafficking of endocytic markers in intestinal cells, and silencing CCT4 in human cells leads to defective endosomal trafficking. These findings highlight the essential role of CCT in regulating vesicle trafficking and provide new insights into its cellular function.
Article
Biochemistry & Molecular Biology
Callista B. Harper, Eva-Maria Blumrich, Michael A. Cousin
Summary: The study highlights the crucial role of the cytoplasmic C terminus of synaptophysin (Syp) in facilitating the accurate retrieval of synaptobrevin-II (SybII) during synaptic vesicle endocytosis. Neurons lacking Syp show defects in SybII retrieval, emphasizing the importance of a conformational change within the Syp C terminus for proper binding and retrieval. Importantly, the study suggests that Syp's presynaptic role is specifically related to the control of SybII retrieval, without affecting the kinetics of synaptic vesicle endocytosis at physiological temperatures.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Nanoscience & Nanotechnology
Jiapei Yang, Li Xu, Ling Di, Yue Su, Xinyuan Zhu
Summary: PEG, as the gold standard for stealth polymer materials, is widely used in drug delivery due to its excellent properties. However, the lack of understanding about the fate of PEG at the cellular level has hindered its application in diagnosis and therapy. Research showed that PEG could be internalized into cells in 1 hour, localized to lysosomes, cytosol, ER, and mitochondria. The fate of PEG in cells could be regulated by conjugating different small molecules, which is crucial for the rational design of PEGylation for drug delivery.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biology
Cansu Kuey, Meghane Sittewelle, Gabrielle Larocque, Miguel Hernandez-Gonzalez, Stephen J. Royle
Summary: This study demonstrates that intracellular clathrin-coated vesicle (CCV) formation can be induced using minimal machinery in living cells, and it can occur on various membranes. The study also shows that the formation of these vesicles, called MitoPits, can faithfully recapitulate all stages of CCV formation without the involvement of accessory proteins.
Review
Biotechnology & Applied Microbiology
Liang Zhang, Xinlin Liang, Tomas Takac, George Komis, Xiaojuan Li, Yuan Zhang, Miroslav Ovecka, Yanmei Chen, Jozef Samaj
Summary: In plants, membrane compartmentalization relies on vesicle trafficking for organelle communication. Membrane proteins involved in vesicle trafficking are dynamic and responsive to environmental changes and cellular signals. Therefore, understanding the localization and dynamics of these proteins is crucial for dissecting vesicular trafficking pathways.
PLANT BIOTECHNOLOGY JOURNAL
(2023)
Article
Cell Biology
Eva-Maria Blumrich, Jessica C. Nicholson-Fish, Marie Pronot, Elizabeth C. Davenport, Dominic Kurian, Adam Cole, Karen J. Smillie, Michael A. Cousin
Summary: Phosphatidylinositol 4-kinase IIa (PI4KIIa) is essential for activity-dependent bulk endocytosis (ADBE) in primary neuronal cultures. The phosphorylation of Ser-47 by glycogen synthase kinase 3(3 (GSK3(3) is crucial for ADBE. Phosphomimetic PI4KIIa interacts with specific presynaptic molecules, including AGAP2 and CAMKV, which are also essential for ADBE when depleted in neurons.
Article
Biochemistry & Molecular Biology
Guan-Ting Liu, Gaga Kochlamazashvili, Dmytro Puchkov, Rainer Mueller, Carsten Schultz, Albert Mackintosh, Dennis Vollweiter, Volker Haucke, Tolga Soykan
Summary: This study reveals the regulatory role of neuronal endosomes in synaptic activity and identifies the importance of endosomal lipid PI(3)P in presynaptic vesicle cycling and neurotransmission.
Review
Plant Sciences
Xiaobo Zhu, Junjie Yin, Hongming Guo, Yuping Wang, Bingtian Ma
Summary: The vesicle trafficking apparatus is crucial for maintaining the homeostasis of membrane-enclosed organelles in eukaryotic cells. Research on vesicle trafficking in plants, particularly rice, is limited, and further investigations are needed to uncover the mysteries of this system.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Cell Biology
Ran Zhao, Yangyang Cao, Yanrui Ge, Jing Xu, Ruofan Li, Mei Yang, Yingying Chen, Dingjie Wu, Jianwei Xiao, Ruili Li
Summary: This study demonstrated that ubiquitination can contribute to the degradation of AMT1;3 proteins under high ammonium stress. Loss of ubiquitination affects the dynamic characteristics and endocytosis of AMT1;3 proteins on the plasma membrane, and inhibits vesicle trafficking pathways under high ammonium conditions. These findings highlight the importance of ubiquitination in the regulation of AMT1;3 proteins.
Article
Neurosciences
Soulmee Koh, Wongyoung Lee, Sang Myun Park, Sung Hyun Kim
Summary: The study demonstrates the important role of Cav1 in synaptic vesicle exocytosis, with its knockdown significantly impairing synaptic vesicle function. Neurons rescued by triple mutants lacking palmitoylation sites of Cav1 show impairments in both synaptic transmission and retrieval, highlighting the importance of Cav1 palmitoylation in activity-driven synaptic vesicle dynamics.
Article
Biochemistry & Molecular Biology
Christiana Kontaxi, Nawon Kim, Michael A. Cousin
Summary: The protein Amph1 plays an important role in coordinating endocytosis in non-neuronal cells and synaptic vesicles at central nerve terminals. It interacts with lipids and proteins, with all interactions except for the PRD domain required for synaptic vesicle endocytosis. This study reveals that the interaction between the PRD domain of Amph1 and endophilin A1 is essential for efficient synaptic vesicle endocytosis.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Cell Biology
Minchuan Zhang, George J. Augustine
Summary: Synaptic vesicles are clustered in presynaptic terminals, with a reserve pool that is mobilized during synaptic activity. Synapsins play a key role in maintaining these vesicles within the reserve pool, potentially by either cross-linking them or creating a liquid phase environment.
Article
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Mohammad-Javad Sanaei, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: Lipid signaling refers to the biological process in which a lipid messenger binds to a protein target, converting its effects to specific cellular responses. The family of phosphoinositide 3-kinase (PI3K) plays a crucial role in this pathway, affecting various aspects of cellular biology such as cell survival, proliferation, migration, endocytosis, intracellular trafficking, metabolism, and autophagy. Different classes of PI3Ks have been identified in yeast and mammals, with class I PI3Ks being extensively studied in cancer biology. Abnormal activation of class I PI3Ks has been implicated in human tumors, particularly through activating mutations in the PIK3CA gene. Class II and III PI3Ks are involved in regulating vesicle trafficking and autophagy processes. This review aims to discuss the latest research findings on PI3Ks-mediated cell biological processes and explore the mechanisms by which different types of phosphoinositides derived from PI3Ks act.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Zuodong Ye, Yiding Xiong, Wang Peng, Wenjie Wei, Lihong Huang, Juliana Yue, Chunyuan Zhang, Ge Lin, Feng Huang, Liang Zhang, Songguo Zheng, Jianbo Yue
Summary: The aberrant regulation of PD-L1 in tumor cells is poorly understood. This study investigates the endosomal trafficking of plasma membrane PD-L1 in tumor cells and demonstrates that it is Rab5- and clathrin-dependent. Triazine compound 6J1 blocks this trafficking and promotes exosomal PD-L1 secretion by activating Rab27. This research provides new insights into the manipulation of PD-L1 endosomal trafficking.
Article
Biochemistry & Molecular Biology
Roya Yousefi, Eugenio F. Fornasiero, Lukas Cyganek, Julio Montoya, Stefan Jakobs, Silvio O. Rizzoli, Peter Rehling, David Pacheu-Grau
Summary: This study developed an imaging approach to analyze mitochondrial translation at the single-cell level, demonstrating the incorporation of clickable non-canonical amino acids to monitor protein expression. The method was successfully applied to various cell types and allowed for spatial resolution monitoring of mitochondrial translation in specialized cells such as cardiomyocytes and neurons. This approach provides new insights into the integration of mitochondrial biogenesis into the cellular context and offers a potential tool for assessing mitochondrial gene expression in mitochondrial diseases.
Article
Biochemical Research Methods
Ivan Silbern, Kuan-Ting Pan, Maksims Fiosins, Stefan Bonn, Silvio O. Rizzoli, Eugenio F. Fornasiero, Henning Urlaub, Reinhard Jahn
Summary: The study investigates the impact of synaptic vesicle cycling-dependent phosphorylation events on various functions in synaptic transmission, including exo- and endocytosis processes.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Clinical Neurology
Margherita Tassan Mazzocco, Fabrizia Claudia Guarnieri, Elena Monzani, Fabio Benfenati, Flavia Valtorta, Stefano Comai
Summary: Deletion of Syns in mice results in behavioral abnormalities and neurobiological changes, including hyperactivity, social impairment, anxiety-like behavior, reduced firing activity of DRN 5-HT neurons, enhanced responsiveness of DRN 5-HT-1A autoreceptors, and lower hippocampal 5-HT levels.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Cell Biology
Bruno Sterlini, Alessandra Romei, Chiara Parodi, Davide Aprile, Michele Oneto, Anita Aperia, Pierluigi Valente, Flavia Valtorta, Anna Fassio, Pietro Baldelli, Fabio Benfenati, Anna Corradi
Summary: This study reveals that PRRT2 deficiency affects the function of Na+/K+ ATPase (NKA) in neurons, leading to increased clustering of NKA on the plasma membrane, which can be reversed by re-expression of PRRT2. Additionally, PRRT2 deficiency also reduces the NKA-dependent afterhyperpolarization in neurons following high-frequency firing.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Maria Regoni, Letizia Zanetti, Stefano Comai, Daniela Mercatelli, Salvatore Novello, Federica Albanese, Laura Croci, Gian Giacomo Consalez, Andrea Ciammola, Flavia Valtorta, Michele Morari, Jenny Sassone
Summary: Mutations in the PARK2 gene cause ARJP, a neurodegenerative disease with no current therapy. The transgenic mouse model ParkinQ311X mimics key features of ARJP, making it a useful tool for studying neurodegenerative mechanisms and screening potential neuroprotective drugs.
Review
Biochemistry & Molecular Biology
Sarva Keihani, Verena Kluever, Eugenio F. Fornasiero
Summary: Long noncoding RNAs (lncRNAs) play crucial roles in regulating neurogenesis, neuronal differentiation, and excitability, making them potential biomarkers for brain diseases due to their diversity and association with neurodegenerative diseases. Further investigation into lncRNA functions is essential for a comprehensive understanding of neuronal pathophysiology in the future.
Article
Cell Biology
Roya Yousefi, Kristina Jevdokimenko, Verena Kluever, David Pacheu-Grau, Eugenio F. Fornasiero
Summary: This study examined two important factors influencing protein turnover: subcellular protein localization and functional state. Using an imaging approach based on pulse-labeling of 17 representative SNAP-tag constructs, precise measurements of protein lifetimes were obtained in various subcellular compartments. The research revealed that changes in protein localization and functional state are key modulators of protein turnover.
Review
Cell Biology
Letizia Zanetti, Maria Regoni, Elena Ratti, Flavia Valtorta, Jenny Sassone
Summary: AMPARs play essential roles in both postsynaptic plasticity and presynaptic neurotransmitter release modulation. Recent studies suggest that presynaptic AMPARs may contribute to axonal pathology, pain transmission regulation, and auditory system physiology. These findings highlight the potential of presynaptic AMPARs as novel pharmacological targets for various pathological conditions.
Article
Clinical Neurology
Stefano Comai, Elisa Melloni, Cristina Lorenzi, Irene Bollettini, Benedetta Vai, Raffaella Zanardi, Cristina Colombo, Flavia Valtorta, Francesco Benedetti, Sara Poletti
Summary: Bipolar disorder (BD) patients showed higher levels of kynurenine (Kyn) and Kyn/tryptophan (Trp) ratio than major depression (MDD) patients, along with lower fractional anisotropy (FA) in several white matter tracts. Lower Trp levels were associated with more severe depressive symptoms and lower FA in specific brain regions, regardless of diagnosis. In BD patients, immune/inflammatory markers were selectively associated with Kyn/Trp ratio, suggesting a potential role of cytokines and Trp conversion into Kyn in affecting white matter microstructure.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fengxia Li, Eugenio F. Fornasiero, Tal M. Dankovich, Verena Kluever, Silvio O. Rizzoli
Summary: By systematically studying probes initially developed for electron microscopy, researchers found that antibodies coupled to 6 nm gold particles exhibit excellent labeling specificity and reliable detection threshold in nanoSIMS imaging. These tools enable accurate visualization and analysis of samples and can be easily combined with other imaging approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Verena Kluever, Belisa Russo, Sunit Mandad, Nisha Hemandhar Kumar, Mihai Alevra, Alessandro Ori, Silvio O. Rizzoli, Henning Urlaub, Anja Schneider, Eugenio F. Fornasiero
Summary: This study investigates the link between physiological aging and neurodegenerative disorders (NDDs) by studying protein turnover. The findings suggest that protein lifetimes are increased in aged brains and aging affects pathways associated with NDDs. A previously unknown alteration in proteostasis was also observed, indicating a metabolic adaptation that may precede neurodegeneration.
Article
Multidisciplinary Sciences
Maxim Katsenelson, Ilana Shapira, Eman Abbas, Kristina Jevdokimenko, Boaz Styr, Antonella Ruggiero, Saba Aid, Eugenio F. Fornasiero, Martin Holzenberger, Silvio O. Rizzoli, Inna Slutsky
Summary: This study reveals that insulin-like growth factor-1 receptor (IGF-1R) is a key regulator of firing rate homeostasis in central neural circuits. At the cellular level, IGF-1R interacts with the mitochondrial calcium uniporter complex (MCUc) and modulates the reliability of burst transfer, thereby affecting firing rate homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Eugenio F. Fornasiero, Jeffrey N. Savas
Summary: The orchestration and regulation of protein production and degradation are central to biological processes. Advances in proteomics have allowed estimation of protein lifetimes and interpretation of proteome changes in development, aging, and disease. This opinion article summarizes techniques, clarifies terminology, and provides insights for interpreting and validating protein turnover measurements. Overall, understanding protein lifetimes is essential for comprehending mammalian biology and defining the processes of life itself.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Sabrina Giofre, Antonio Renda, Silvia Sesana, Beatrice Formicola, Barbara Vergani, Biagio Eugenio Leone, Vanna Denti, Giuseppe Paglia, Serena Groppuso, Valentina Romeo, Luca Muzio, Andrea Balboni, Andrea Menegon, Antonia Antoniou, Arianna Amenta, Daniele Passarella, Pierfausto Seneci, Sara Pellegrino, Francesca Re
Summary: Dual functionalized liposomes with modified peptides and MMP-sensitive moieties have the ability to cross BBB and release drugs in MMP-rich microenvironment. These liposomes display good biocompatibility and efficiently release encapsulated fluorescent dyes.
Editorial Material
Biochemistry & Molecular Biology
Eugenio F. Fornasiero