Article
Biochemistry & Molecular Biology
Tapojyoti Das, Meraj Ramezani, David Snead, Cristian Follmer, Peter Chung, Ka Yee Lee, David A. A. Holowka, Barbara A. A. Baird, David Eliezer
Summary: Alpha-synuclein plays an important role in regulating synaptic vesicle cycling, exerting both inhibitory and potentiating effects on vesicle release. The binding affinity of alpha-synuclein to isolated vesicles is a key determinant of its ability to potentiate release.
Review
Cell Biology
Sofiia Reshetniak, Silvio O. Rizzoli
Summary: The synaptic vesicle cluster is not only a storage space for synaptic vesicles, but also potentially regulates protein distribution, cytoskeleton architecture, selective removal of synaptic components, and presynaptic responses to plasticity. It serves as a key organizer of synaptic composition and dynamics.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christian Hoffmann, Roberto Sansevrino, Giuseppe Morabito, Chinyere Logan, R. Martin Vabulas, Ayse Ulusoy, Marcelo Ganzella, Dragomir Milovanovic
Summary: The regulation of neurotransmission relies on the interaction between synapsin and alpha-synuclein, with the presence of synaptic vesicles enhancing their condensation into functional clusters. The molar ratio between synapsin and alpha-synuclein is crucial for the formation of these clusters and understanding their molecular mechanisms is important for clarifying the pathogenesis of synucleinopathies.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuai Huang, Bingkuan Xu, Yinghui Liu
Summary: This study reveals that Ca2+ accelerates the amyloid aggregation of α-Syn through the modulation of protein phase separation. Ca2+ promotes the formation of α-Syn liquid droplets and enables their fusion with other droplets. The enlargement of Ca2+-induced α-Syn droplets can be eliminated by a metal chelator. Interestingly, Ca2+ still promotes α-Syn phase separation in the presence of lipid membranes and facilitates the recruitment of lipid vesicles to the surface of these condensates.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Neurosciences
Goeun Kim, Sang-Eun Lee, Seonyoung Jeong, Jeongkun Lee, Daehun Park, Sunghoe Chang
Summary: The coacervation between Syph and Syn is primarily driven by multivalent pi-cation electrostatic interactions among tyrosine residues of Syph C-terminal and positively charged Syn. Mutating the critical tyrosine residues to serine completely abolished the phase separating property of Syph Ct, indicating the importance of tyrosine-mediated pi-interactions. The results suggest that pi-cation interactions rather than simple charge interactions are responsible for their coacervation.
Article
Biochemistry & Molecular Biology
Bingkuan Xu, Fengshuo Fan, Yunpeng Liu, Yinghui Liu, Lin Zhou, Haijia Yu
Summary: Lewy bodies and Lewy neurites are key pathological hallmarks of Parkinson's disease, with alpha-Synuclein (alpha-Syn) aggregation playing a crucial role. Mutations associated with familial PD affect alpha-Syn LLPS and its correlation with amyloid aggregation, but the exact mechanisms remain unclear.
Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Parkinson's disease is characterized by the degeneration of dopaminergic neurons and the accumulation of Lewy bodies. Previous studies have examined the molecular mechanism linking nitroxidation, aS aggregation, and PD, but the impact of nitroxidation on the physiological function of aS was unclear. Our research found that nitroxidation of Y39 lengthened the disordered stretch between two consecutive alpha-helices and prevented aS from functioning as a catalyst for the clustering and fusion of synaptic vesicles.
Article
Biochemistry & Molecular Biology
Anna Siegert, Marija Rankovic, Filippo Favretto, Tina Ukmar-Godec, Timo Strohaeker, Stefan Becker, Markus Zweckstetter
Summary: In patients with Parkinson's disease and dementia, interactions between tau protein pathology and alpha-synuclein pathology may have synergistic effects, contributing to a worse prognosis. Understanding the mechanisms of this interaction can help clarify the relationship between these two distinct pathologies.
Article
Cell Biology
Benjamin Feller, Aurelie Fallon, Wen Luo, Phuong Trang Nguyen, Irina Shlaifer, Alfred Kihoon Lee, Nicolas Chofflet, Nayoung Yi, Husam Khaled, Samer Karkout, Steve Bourgault, Thomas M. Durcan, Hideto Takahashi
Summary: This study shows that beta-isoforms of neurexins (beta-NRXs) interact with alpha-syn preformed fibrils (alpha-syn PFFs) to inhibit beta-NRX-mediated presynaptic organization, providing new insights into the molecular mechanism of synaptic pathology induced by alpha-syn PFFs in synucleinopathies such as Parkinson's disease and dementia with Lewy bodies.
Review
Physiology
Tomohisa Hosokawa, Pin-Wu Liu
Summary: Synaptic plasticity is a cellular mechanism crucial for learning and memory, involving the regulation of synaptic strength and organization of AMPAR on the postsynaptic membrane. PSD regulates AMPAR dynamics through LLPS to enhance synaptic transmission efficacy. The formation of nanodomains via LLPS protein condensates is important for synaptic plasticity.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sophia M. McClain, Moses H. Milchberg, Chad M. Rienstra, Catherine J. Murphy
Summary: The interaction between alpha-synuclein and synaptic vesicle mimics depends on the malleability and rigidity of the mimics, with higher binding affinities observed for rigid mimics. The lipid composition of the mimics also affects the interaction. The study provides insights into the behavior of alpha-synuclein and its relation to membrane properties.
Review
Biochemical Research Methods
Rita Pancsa, Wim Vranken, Balint Meszaros
Summary: The study of membraneless organelles formed via liquid-liquid phase separation is a fascinating field in current molecular biology. Researchers are continuously developing and optimizing in vitro and in vivo methods to identify and characterize these molecular condensates as well as the proteins involved in liquid-liquid phase separation.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Human alpha-synuclein (α S) is an intrinsically disordered protein highly expressed in dopaminergic neurons. Its amyloid aggregates are considered a hallmark of Parkinson's disease (PD). The oxidation of alpha S's methionine residues (MetO) affects its affinity towards anionic micelles and synaptic-like vesicles, impairing its physiological function as a catalyst of vesicle clustering and fusion.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Biochemistry & Molecular Biology
Phoebe S. Tsoi, My Diem Quan, Josephine C. Ferreon, Allan Chris M. Ferreon
Summary: Cellular deposition of protein aggregates disrupts cellular functions and leads to neuronal death. Understanding the role of protein misfolding and aggregation provides insights into neurodegenerative diseases and their common underlying molecular pathology. The major proteins involved in neurodegeneration, such as amyloid beta, tau, alpha-synuclein, and TAR DNA-binding protein, possess enhanced ability to partition into biomolecular condensates and are described as intrinsically disordered.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Marianna Decet, Patrik Verstreken
Summary: Autophagy is a crucial catabolic pathway for maintaining cellular homeostasis by degrading defective proteins and organelles. In neurons, the orchestrated progression of autophagy takes place in distinct subcellular compartments. Autophagy is essential for proper synaptic function and neuronal survival, particularly in the face of challenges like distance from the soma and oxidative stress.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dragomir Milovanovic, Mitja Platen, Meike Junius, Ulf Diederichsen, Iwan A. T. Schaap, Alf Honigmann, Reinhard Jahn, Geert van den Bogaart
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Review
Neurosciences
Dragomir Milovanovic, Pietro De Camilli
Article
Multidisciplinary Sciences
Dragomir Milovanovic, Yumei Wu, Xin Bian, Pietro De Camilli
Editorial Material
Cell Biology
Christian Hoffmann, Dragomir Milovanovic
Article
Multidisciplinary Sciences
Daehun Park, Yumei Wu, Sang-Eun Lee, Goeun Kim, Seonyoung Jeong, Dragomir Milovanovic, Pietro De Camilli, Sunghoe Chang
Summary: The combination of synapsin and synaptophysin proteins in fibroblasts efficiently reconstitutes synaptic vesicle clusters with similar morphology and liquid-like properties to those found at synapses, suggesting they play a key role in the assembly of synaptic structures.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Eleonora Perego, Sofiia Reshetniak, Charlotta Lorenz, Christian Hoffmann, Dragomir Milovanovic, Silvio O. Rizzoli, Sarah Koester
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Christian Hoffmann, Roberto Sansevrino, Giuseppe Morabito, Chinyere Logan, R. Martin Vabulas, Ayse Ulusoy, Marcelo Ganzella, Dragomir Milovanovic
Summary: The regulation of neurotransmission relies on the interaction between synapsin and alpha-synuclein, with the presence of synaptic vesicles enhancing their condensation into functional clusters. The molar ratio between synapsin and alpha-synuclein is crucial for the formation of these clusters and understanding their molecular mechanisms is important for clarifying the pathogenesis of synucleinopathies.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Correction
Cell Biology
Christian Hoffmann, Dragomir Milovanovic
Review
Cell Biology
Katarina Milicevic, Branislava Rankovic, Pavle R. Andjus, Danijela Bataveljic, Dragomir Milovanovic
Summary: Liquid-liquid phase separation (LLPS) is an important principle for the organization of biomolecular condensates in neurons and glia. Misregulation of condensates in neurodegenerative diseases like ALS leads to protein aggregation and affects cellular function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Franziska Trnka, Christian Hoffmann, Han Wang, Roberto Sansevrino, Branislava Rankovic, Benjamin R. Rost, Dietmar Schmitz, H. Broder Schmidt, Dragomir Milovanovic
Summary: Research suggests that high expression levels play a dominant role in determining the fraction of cells with soluble or aggregated FUS, whether wild-type or mutant. Chemically induced FUS aggregates recruit LAMP1-positive structures, while mature, acidic lysosomes only accumulate at FUS aggregates but not at liquid condensates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Kiara Freitag, Nele Sterczyk, Sarah Wendlinger, Benedikt Obermayer, Julia Schulz, Vadim Farztdinov, Michael Muelleder, Markus Ralser, Judith Houtman, Lara Fleck, Caroline Braeuning, Roberto Sansevrino, Christian Hoffmann, Dragomir Milovanovic, Stephan J. Sigrist, Thomas Conrad, Dieter Beule, Frank L. Heppner, Marina Jendrach
Summary: The study found that spermidine can reduce neurotoxic soluble A beta and decrease AD-associated neuroinflammation in amyloid prone AD-like APPPS1 mice, mainly targeting AD-associated microglia and affecting cell migration and phagocytosis gene expression.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Neurosciences
Roberto Sansevrino, Christian Hoffmann, Dragomir Milovanovic
Summary: Neuronal communication relies on the exocytosis of neurotransmitters from clustered synaptic vesicles (SVs) at synapses. Synapsin 1, an abundant SV-associated phosphoprotein, has been established to be responsible for the clustering of SVs through protein-protein interactions. Recent studies have discovered that synapsins can cluster SVs through liquid-liquid phase separation (LLPS), presenting a new framework for understanding synaptic organization. This article discusses the evidence for SV phase separation and raises questions regarding its regulation, specificity, and reversibility.
TRENDS IN NEUROSCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Christian Hoffmann, Gennadiy Murastov, Johannes Vincent Tromm, Jean-Baptiste Moog, Muhammad Awais Aslam, Aleksandar Matkovic, Dragomir Milovanovic
Summary: In this study, graphene-based sensors were used to investigate the electrostatic properties of synapsin condensates. It was found that synapsin condensates generate strong electrical responses when in contact with graphene, and this electrical response is caused by the formation of an electric double layer between the condensates and graphene.
Article
Biophysics
Huan Wang, Fleurie M. Kelley, Dragomir Milovanovic, Benjamin S. Schuster, Zheng Shi
Summary: A unique micropipette-based technique was developed to quantify both the surface tension and viscosity of biomolecular condensates, independent of labeling and surface-wetting effects. The accuracy and versatility of this technique were demonstrated by measuring different types of biomolecular condensates in experiments, confirming its effectiveness in studying condensate material properties.
BIOPHYSICAL REPORTS
(2021)
