Article
Cell Biology
May Bakr, Damien Jullie, Julia Krapivkina, Vincent Paget-Blanc, Lou Bouit, Jennifer D. Petersen, Natacha Retailleau, Christelle Breillat, Etienne Herzog, Daniel Choquet, David Perrais
Summary: The study identifies VAMP4 as the vesicular SNARE that mediates most dendritic recycling endosome exocytosis, while VAMP2 plays a minor role in this process. Knock down of VAMP4 reduces TfR recycling but increases AMPAR recycling, leading to increased AMPAR-mediated synaptic transmission and occlusion of LTP expression. The opposing changes in AMPAR and TfR recycling upon VAMP4 knock down reveal their sorting into separate endosomal populations.
Article
Multidisciplinary Sciences
Jie Yang, Huaizhou Jin, Yihao Liu, Yaya Guo, Yongli Zhang
Summary: Munc18 chaperones play a key role in mediating membrane fusion between vesicles and plasma membranes. Recent studies have revealed that Munc18-1 and Munc18-3 form ternary complexes with their cognate SNAREs, which facilitate the binding of SNAP-25 or SNAP-23 to conclude SNARE assembly. This study provides further insights into the structure, dynamics, and function of these template complexes. Our findings demonstrate that a highly dynamic template complex mediates efficient and specific SNARE assembly.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Viktoria Szentgyoergyi, Anne Spang
Summary: Cargo delivery in cellular organelles relies on the fusion of vesicles with the help of tethering factors. Recent studies show that tethers play a significant role in membrane fusion, and the discovery of novel tether FERARI complex has changed our understanding of cargo transport.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Chuqi Liu, Dexiang Liu, Shen Wang, Lu Gan, Xiangliang Yang, Cong Ma
Summary: Exosomes play crucial roles in cellular communication and tumorigenesis. This study identifies SNARE proteins as the key regulators of exosome secretion in breast cancer cells and demonstrates their conserved function in different cancer types. Furthermore, targeting VAMP-7 may hold promise as a therapeutic strategy for breast cancer.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Chemistry, Multidisciplinary
Md Mofizur Rahman, Mohammed A. Abosheasha, Yoshihiro Ito, Motoki Ueda
Summary: Peptide-lipid hybrid vesicles were prepared by incorporating complementary DNA strands in their lipid domains. Controlled fusion of the vesicles was induced through hybridization of the complementary DNA strands during repeated heating and cooling cycles. The decrease in Forster resonance energy transfer efficiency and transmission electron microscopy analysis confirmed the presence of vesicle fusion. This approach provides a general strategy for the creation of polymersomes with membrane-fusion functionality.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biophysics
Lanxi Wu, Kevin C. Courtney, Edwin R. Chapman
Summary: The study demonstrates that cholesterol dramatically stabilizes fusion pores in the open state, resulting in a significant increase in the open dwell-time. This effect is attributed to the known role of cholesterol in altering the elastic properties of lipid bilayers.
BIOPHYSICAL JOURNAL
(2021)
Article
Neurosciences
Femke M. Feringa, Annemiek A. van Berkel, Anushka Nair, Matthijs Verhage
Summary: Depletion of presynaptic proteins MUNC18-1 or syntaxin-1 triggers an atypical, staged cell death pathway characterized by consecutive neurite retraction, ultimately leading to, but not driven by, apoptosis.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Yan Zhang, Yaru Hu, Huayong Xie, Maili Liu, Jun Yang, Cong Ma
Summary: This study characterized the conformation of Syb-2 in different assembly states using solid-state NMR experiments and found that it has a highly dynamic nature and α-helical contents. The coupling between Syb-2 and Syx-1 TMDs, as well as the high mobility of the C-terminal segment of Syb-2 TMD, were identified as crucial for inner membrane merger. These findings provide new insights into the role of Syb-2 TMD in membrane fusion and improve the understanding of the structural mechanism of SNARE complex assembly. The study highlights the significance of membrane environments in elucidating the mechanism of membrane proteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Biochemistry & Molecular Biology
Mikhail Khvotchev, Mikhail Soloviev
Summary: In this review, the recent advances in the development of functional peptides that can modify SNARE-binding interfaces and modulate SNARE function are discussed. The authors evaluate two systems based on peptide-nucleic acids (PNAs) and coiled coil peptides, and review how the self-assembly of SNARE motifs can be used to drive the assembly of complex re-engineered polypeptides.
Article
Chemistry, Physical
Bence Feher, Levena Gascoigne, Sanne N. Giezen, Ilja K. Voets
Summary: Membrane fusion plays a vital role in biological processes such as cellular uptake, cell communication, and RNA delivery. This study focuses on the role of coiled-coil (CC) peptides, particularly the E-K complex, in membrane fusion. By substituting lysine amino acids with arginine at different positions in the peptide sequence, the researchers found that increasing the amount of arginine enhances the peptide's affinity to the membrane. Molecular dynamics simulations and coarse-grained simulations also showed that the interaction between the peptides and the membrane triggers increased membrane curvature without disrupting lipid packing. Furthermore, all modified peptides retained the ability to form CC complexes with E peptides. The findings suggest that the positioning of arginine is critical when designing CC fusion peptides. Peptides with arginines located at the N-terminus exhibit greater affinity to the lipid membrane. Introducing arginine into CC peptide sequences can enhance binding affinity to the membrane and may lead to more effective CC fusion peptides than the E-K complexes.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Article
Biochemistry & Molecular Biology
Wei Li, Ying Xing, Yue Wang, Tao Xu, Eli Song, Wei Feng
Summary: As the prototype of Sec1/Munc18 (SM) family proteins, Munc18-1 can control intracellular membrane fusion by manipulating the distinct conformations of syntaxin-1. The structure of the Mint1-MID-Munc18-1-syntaxin-1 complex is determined, revealing that Munc18-1 recognizes Mint1-MID and syntaxin-1 simultaneously via two opposite sites.
Article
Virology
Sourav Haldar, Kenta Okamoto, Rebecca A. Dunning, Peter M. Kasson
Summary: The study focused on the chemically controllable triggering of single-virus fusion within endosomes. The results showed that endosomal curvature did not significantly affect fusion kinetics, indicating that membrane deformability may play a more crucial role in viral entry. This study provides insights into how cellular restriction factors and altered endosomal trafficking affect viral membrane fusion.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Hong Huang, Qinqin Ouyang, Kunrong Mei, Ting Liu, Qiming Sun, Wei Liu, Rong Liu
Summary: This study reveals that both acetylation and phosphorylation modifications control the function of SCFD1 in autophagosome-lysosome fusion. KAT2B/PCAF catalyzes the acetylation of SCFD1, while SIRT4 deacetylates it. Additionally, AMPK-controlled phosphorylation disrupts the interaction between SCFD1 and KAT2B and inhibits SCFD1 acetylation. Furthermore, SCFD1 acetylation inhibits autophagic flux by blocking SNARE complex formation.
Review
Cell Biology
Xiaoyu Tian, Junlin Teng, Jianguo Chen
Summary: Macroautophagy/autophagy is a cellular mechanism for the degradation of cellular contents, with the final step being the fusion of autophagosome with the lysosome mediated by SNARE proteins. In addition to regulating autophagosome-lysosome fusion, some SNAREs are also involved in other autophagic processes, controlling fusion process spatially and temporally.
Letter
Hematology
James A. Poulter, Jason C. Collins, Catherine Cargo, Ruth M. De Tute, Paul Evans, Daniela Ospina Cardona, David T. Bowen, Joanna R. Cunnington, Elaine Baguley, Mark Quinn, Michael Green, Dennis McGonagle, David B. Beck, Achim Werner, Sinisa Savic
Review
Biophysics
Tobias Grothe, Julia Nowak, Reinhard Jahn, Peter Jomo Walla
Summary: The passage describes various fluorescence-based methods developed over the past decade to monitor membrane fusion, docking, distances, and curvature. These tools were primarily developed using liposomes as model systems, and their application range and limitations are discussed with examples from protein-mediated vesicle docking and fusion studies.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Judyta K. Juranek, Konark Mukherjee, Reinhard Jahn, Jia-Yi Li
Summary: Synaptic transmission relies on neurotransmitters stored in synaptic vesicles and released at the active zone. Research shows a robust bi-directional, coordinated trafficking of synaptic vesicle and active zone proteins in peripheral nerves, which plays a critical role in neuronal function and neurodegenerative diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Agata Witkowska, Leonard P. Heinz, Helmut Grubmueller, Reinhard Jahn
Summary: Proteins driving membrane fusion must overcome energy barriers to induce intermediate steps where lipid bilayers' integrity is lost. The metastable intermediate preceding hemifusion does not require but is enhanced by divalent cations, characterized by the absence of proteins and local membrane thickening, induced by lipid rearrangements due to dehydration of the membrane surface revealed by simulations.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Changwon Kim, Min Ju Shon, Sung Hyun Kim, Gee Sung Eun, Je-Kyung Ryu, Changbong Hyeon, Reinhard Jahn, Tae-Young Yoon
Summary: Using single-molecule methods, researchers demonstrated the cooperativity between NSF and the SNARE complex to prevent ATP consumption without productive disassembly.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Seiichi Koike, Reinhard Jahn
Summary: Membrane traffic in eukaryotic cells is regulated by transport vesicles that contain targeting signals recognized by tethering factors. The final step, membrane fusion, is mediated by SNARE proteins. The role of SNARE proteins in targeting specificity is still a topic of debate.
BIOCHEMICAL JOURNAL
(2022)
Article
Peripheral Vascular Disease
Harish E. Chatrathi, Jason C. Collins, Lynne A. Wolfe, Thomas C. Markello, David R. Adams, William A. Gahl, Achim Werner, Prashant Sharma
Summary: This study identifies a novel CUL3 variant in a patient with familial hyperkalemic hypertension, and reveals the molecular mechanisms by which this variant leads to dysregulation of the CUL3-KLHL3-WNK signaling pathway.
Review
Rheumatology
David B. Beck, Achim Werner, Daniel L. Kastner, Ivona Aksentijevich
Summary: Ubiquitylation is a crucial post-translational modification that regulates intracellular signaling pathways. It plays a key role in innate immune responses and is associated with various genetic disorders and autoinflammatory diseases.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Hematology
Marcela A. Ferrada, Sinisa Savic, Daniela Ospina Cardona, Jason C. Collins, Hugh Alessi, Fernanda Gutierrez-Rodrigues, Dinesh Babu Uthaya Kumar, Lorena Wilson, Wendy Goodspeed, James S. Topilow, Julie J. Paik, James A. Poulter, Tanaz A. Kermani, Matthew J. Koster, Kenneth J. Warrington, Catherine Cargo, Rachel S. Tattersall, Christopher J. A. Duncan, Anna Cantor, Patrycja Hoffmann, Elspeth M. Payne, Hanna Bonnekoh, Karoline Krause, Edward W. Cowen, Katherine R. Calvo, Bhavisha A. Patel, Amanda K. Ombrello, Daniel L. Kastner, Neal S. Young, Achim Werner, Peter C. Grayson, David B. Beck
Summary: Somatic mutations in UBA1 cause VEXAS syndrome, an adult-onset inflammatory disease with high mortality and clinical heterogeneity. Ear chondritis is associated with increased survival, while transfusion dependence and specific gene variants are associated with decreased survival. The study demonstrates the impact of gene mutations on translation and survival rate.
Meeting Abstract
Hematology
Jason C. Collins, Nicholas Balanda, Samuel J. Magaziner, Maya English, Daniela Ospina Cardona, Mrinal M. Patnaik, Benjamin Terrier, Olivier Kosmider, Achim Werner, David B. Beck
Article
Biochemistry & Molecular Biology
Francois Le Guerroue, Eric N. Bunker, William M. Rosencrans, Jack T. Nguyen, Mohammed A. Basar, Achim Werner, Tsui-Fen Chou, Chunxin Wang, Richard J. Youle
Summary: This study reveals that TNIP1 acts as a negative regulator of mitophagy, which is a selective autophagy process. TNIP1 interacts with the LC3/GABARAP family of proteins and the autophagy receptor TAX1BP1, and competes with autophagy receptors by binding with the ULK1 complex member FIP200. These findings provide insights into the early steps of autophagosome biogenesis during mitophagy.
Article
Rheumatology
Blanka Stiburkova, Katerina Pavelcova, Monika Belickova, Samuel J. Magaziner, Jason C. Collins, Achim Werner, David B. Beck, Veronika Balajkova, Cyril Salek, Martin Vostry, Herman Mann, Jiri Vencovsky
Summary: This study reports a case of a European ancestry patient with clinical manifestations of VEXAS syndrome associated with a newly identified dysfunctional UBA-1 enzyme variant. Due to the patient's insufficient response to various immunosuppressive treatments, allogeneic hematopoietic stem cell transplantation was performed, which resulted in significant improvement of clinical and laboratory manifestations of the disease.
ARTHRITIS & RHEUMATOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Aparna Baxi, Achim Werner
Article
Biochemistry & Molecular Biology
Eric N. Bunker, Francois Le Guerroue, Chunxin Wang, Marie-Paule Strub, Achim Werner, Nico Tjandra, Richard J. Youle
Summary: This study reveals the mechanisms of Nix-mediated mitophagy and the importance of both the LIR and MER regions. The MER region interacts with the autophagy effector WIPI2 and recruits it to mitochondria, while the LIR region converts the distribution of WIPI2 on mitochondria into puncta. These findings provide valuable insights into the process of Nix-induced mitophagy.
Review
Cell Biology
Reinhard Jahn, David C. Cafiso, Lukas K. Tamm
Summary: This article reviews the SNARE-mediated fusion pathway, including the assembly of SNARE proteins into complexes, the regulation of this assembly by accessory proteins, and the overcoming of energy barriers that prevent membrane fusion.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)