Review
Cell Biology
Huili Li, Ruijuan Guo, Yun Guan, Junfa Li, Yun Wang
Summary: Synapses in the central nervous system are dynamic and highly plastic interfaces for information transmission between neurons. Trans-synaptic cell-adhesion molecules, such as neurexins and neuroligins, regulate the assembly of synaptic molecules and play a role in synaptopathies associated with pathological pain.
Review
Neurosciences
Dongseok Lim, Dongwook Kim, Ji Won Um, Jaewon Ko
Summary: This article discusses how multiple synaptic adhesion proteins collectively define the properties of specific synapses and shape the architectures of neural circuits. While there is growing evidence supporting a molecular model, there are still some fundamental open questions that need to be addressed in future research.
TRENDS IN NEUROSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kaiyu Xue, Yunyun Hu, Shuanglin Gu, Chao Wang, Ren Kong, Wei Xie, Jian Li
Summary: The synapse is a specialized structure regulating neurotransmission, with cell adhesion molecules playing key roles in cell interactions. NRXNs and NLGNs are associated with autism and other neuropsychiatric diseases, with numerous variants identified in previous research. By analyzing protein structures and using risk assessment tools, potential pathological variants were identified for further investigation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Nanoscience & Nanotechnology
Joohee Jeon, Sun-heui Yoon, Min-Ah Oh, Wonkyung Cho, Ji Yong Kim, Chang Il Shin, Eun Joong Kim, Taek Dong Chung
Summary: The coordination of synapses onto electrodes with high specificity is crucial, and using neuroligin-1 protein on electrode surfaces can lead to the formation of synapses with type specificity and structural robustness. This approach may open up new possibilities in interfacing neural circuitry with electronics.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Review
Biochemistry & Molecular Biology
Katelyn Cuttler, Maryam Hassan, Jonathan Carr, Ruben Cloete, Soraya Bardien
Summary: Synaptopathies are brain disorders characterized by dysfunctional synapses, which are essential for transmitting information between neurons. Neurexins, a type of synaptic cell adhesion molecule, have gained interest due to their association with neuropsychiatric disorders and neurodegenerative disorders. Both changes in neurexin expression and mutations have been implicated in diseases such as autism spectrum disorder and Parkinson's disease.
Article
Biochemistry & Molecular Biology
Nan Yagishita-Kyo, Yuki Ikai, Tomoko Uekita, Akio Shinohara, Chihiro Koshimoto, Keisuke Yoshikawa, Kei Maruyama, Sosuke Yagishita
Summary: Octodon degus is considered one of the most human-like rodents with enhanced cognitive function. Cloning and characterizing sociality-related genes in degus, the study found high similarity between degus Neuroligin4 and human Neuroligin4X, unlike in mice. Furthermore, testosterone was shown to bind to degus Neurexin and disrupt intercellular binding, potentially influencing the incidence of autism in males.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Tomoyuki Yoshida, Atsushi Yamagata, Ayako Imai, Juhyon Kim, Hironori Izumi, Shogo Nakashima, Tomoko Shiroshima, Asami Maeda, Shiho Iwasawa-Okamoto, Kenji Azechi, Fumina Osaka, Takashi Saitoh, Katsumi Maenaka, Takashi Shimada, Yuko Fukata, Masaki Fukata, Jumpei Matsumoto, Hisao Nishijo, Keizo Takao, Shinji Tanaka, Shigeo Okabe, Katsuhiko Tabuchi, Takeshi Uemura, Masayoshi Mishina, Hisashi Mori, Shuya Fukai
Summary: Mutations of Neuroligin 3 (NLGN3) have been linked to autism spectrum disorder (ASD). Researchers have identified a new interaction between NLGN3 and a splice variant of protein tyrosine phosphatase delta (PTP delta) and its impact on social behavior development in mice. The study suggests that both canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sarah D. Ackerman, Nelson A. Perez-Catalan, Marc R. Freeman, Chris Q. Doe
Summary: The study identifies a critical period in a developing Drosophila motor circuit and demonstrates the essential role of astrocytes in proper critical period termination. Changes in activity during the critical period regulate dendrite length, complexity, and connectivity of motor neurons, while astrocyte ablation prolongs this critical period. Additionally, genetic screening reveals astrocyte-motor neuron signaling pathways that ensure timely critical period closure and proper locomotor behavior.
Article
Neurosciences
Christabel X. Tan, Cagla Eroglu
Summary: Astrocytes play a key role in regulating synapse formation and function by interacting with neuronal synapses at tripartite synapses. Recent studies have shown a diverse range of cell adhesion-based mechanisms that mediate astrocyte-synapse interactions and influence both astrocyte morphological maturation and synapse development. These newly discovered molecular pathways in brain physiology have implications for both health and disease.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Cell Biology
Emma E. Boxer, Charlotte Seng, David Lukacsovich, JungMin Kim, Samantha Schwartz, Matthew J. Kennedy, Csaba Foldy, Jason Aoto
Summary: The study reveals multiple roles for Nrxn3 at GABAergic synapses in vSUB, showing sexually dimorphic intrinsic connectivity and synaptic function. While PVs preferentially contact RS neurons in male mice, they favor BS neurons in female mice. Nrxn3 knockout affects synapse density and postsynaptic strength in males, but enhances presynaptic release in females.
Article
Multidisciplinary Sciences
Hau B. Nguyen, Thomas C. Terwilliger, Geoffrey S. Waldo
Summary: Research has shown the utility of split fluorescent proteins for large scale protein labeling in cells, but efficient split fluorescent proteins that do not cross-react are needed for multiplexing experiments. The newly proposed split ccGFP from C. californica complements up to threefold faster compared to the original A. victoria split GFP, enabling multiplexed labeling with existing A. victoria split YFP and CFP.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Yichen Sun, Moyi Li, Junhua Geng, Sibie Meng, Renjun Tu, Yan Zhuang, Mingkuan Sun, Menglong Rui, Mengzhu Ou, Guangling Xing, Travis K. Johnson, Wei Xie
Summary: Neuroligins, through an interaction between DNlg2 and RACK1, regulate F-Actin assembly at the Drosophila NMJ via the Cofilin signaling pathway. Deletion of DNlg2 disrupts the actin cytoskeleton and results in abnormal synaptic transmission and locomotion. Overexpression of certain forms of Cofilin can rescue these defects. These findings highlight the importance and complexity of Neuroligins in neural connectivity.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shanghua Fan, Shanti Pal Gangwar, Mischa Machius, Gabby Rudenko
Summary: This study reveals the molecular basis of a regulatory network formed by the proteins Hevin, SPARC, and MDGA, showing that Hevin competes with SPARC and MDGA to regulate synaptogenic effects and extracellular matrix interactions by binding to overlapping sites on neuroligin.
Article
Neurosciences
Shuting Chen, Anand Venkatesan, Yong Qi Lin, Jing Xie, Gregory Neely, Swati Banerjee, Manzoor A. Bhat
Summary: MEGF8 is a highly conserved transmembrane protein that is associated with genetic disorders and psychiatric disorders. This study shows that dMegf8 plays a crucial role in synaptic growth and neurotransmission in fruit flies, and its mutation leads to motor coordination deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Ki Sung Park, Ryeo Gang Son, Sung Ho Kim, Mohamed A. A. Abdelhamid, Seung Pil Pack
Summary: In this study, we successfully prepared split GFP1-9 with improved expression levels and solubility using Escherichia coli as host. The purified split GFP1-9 showed high solubility and a significant increase in expression yield compared to refolded split GFP1-9. The use of this improved split GFP1-9 enables high fluorescence recovery yield, making it suitable for in vitro reconstitution-based applications such as protein-protein interaction analysis or biosensing system design.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Yousuf A. Khan, K. Ian White, Axel T. Brunger
Summary: ATPases associated with diverse cellular activities (AAA+ proteins) are a superfamily of proteins that are found in all domains of life, transducing chemical energy into mechanical energy through ATP hydrolysis. They perform various cellular functions, including protein disassembly, quality control, DNA replication, and viral replication. Understanding the conserved mechanisms of AAA+ proteins is crucial for health and disease.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Letter
Multidisciplinary Sciences
Peter B. Moore, Wayne A. Hendrickson, Richard Henderson, Axel T. Brunger
Article
Biochemistry & Molecular Biology
John Jacob Peters, Jeremy Leitz, Qiang Guo, Florian Beck, Wolfgang Baumeister, Axel T. Brunger
Summary: Advancements in electron microscope technology and data processing have enabled the visualization of molecules and complexes in their natural environment, with methods such as feature-guided subtomogram alignment and 3D signal permutation leading to improved subtomogram average maps for datasets of synaptic protein complexes.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ana L. Moreno-Salinas, Brian J. Holleran, Estefania Y. Ojeda-Muniz, Kerlys G. Correoso-Brana, Sheila Ribalta-Mena, Jose-Carlos Ovando-Zambrano, Richard Leduc, Antony A. Boucard
Summary: Research has uncovered genetic variants in the Lphn3 gene that are associated with ADHD. These variants affect the function of the Lphn3 receptor, particularly its coupling with G protein signaling. These findings provide new insights into the pathogenesis of ADHD.
MOLECULAR PSYCHIATRY
(2022)
Editorial Material
Multidisciplinary Sciences
Antony A. Boucard
Article
Multidisciplinary Sciences
Ying Lai, Giorgio Fois, Jose R. Flores, Michael J. Tuvim, Qiangjun Zhou, Kailu Yang, Jeremy Leitz, John Peters, Yunxiang Zhang, Richard A. Pfuetzner, Luis Esquivies, Philip Jones, Manfred Frick, Burton F. Dickey, Axel T. Brunger
Summary: Membrane fusion triggered by Ca2+ is important for synaptic neurotransmitter release and mucin secretion. A designed peptide can disrupt Ca2+-triggered membrane fusion, reduce stimulated mucin secretion, and alleviate mucus occlusion of mouse airways.
Article
Multidisciplinary Sciences
Kailu Yang, Chuchu Wang, K. Ian White, Richard A. Pfuetzner, Luis Esquivies, Axel T. Brunger
Summary: Variants of SARS-CoV-2 challenge current COVID-19 vaccines and antibody therapies. Mutations in the viral spike glycoprotein impact the fusion process, but do not alter the overall structure of the viral bundle. Targeting the interface between HR1 and HR2 could be an effective strategy for developing antiviral inhibitors against all known SARS-CoV-2 variants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Ying Lai, Michael J. Tuvim, Jeremy Leitz, John Peters, Richard A. Pfuetzner, Luis Esquivies, Qiangjun Zhou, Barbara Czako, Jason B. Cross, Philip Jones, Burton F. Dickey, Axel T. Brunger
Summary: The primary interface between the SNARE complex and synaptotagmin-1 is crucial for Ca2+-triggered neurotransmitter release and is conserved across species. In this study, hydrocarbon-stapled peptides were designed to interfere with the primary interface and were found to inhibit both Ca2+-independent and Ca2+-triggered release. These peptides have the potential to combat excessive mucus secretion in respiratory diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Monserrat Avila-Zozaya, Brenda Rodriguez-Hernandez, Feliciano Monterrubio-Ledezma, Bulmaro Cisneros, Antony A. Boucard
Summary: The study revealed that cancer progression relies on cellular transition states accompanied by changes in the functionality of adhesion molecules. The mutations in the adhesion G protein-coupled receptor latrophilin-3 (aGPCR Lphn3) affected the intercellular adhesion profile and led to aberrant remodeling of vimentin, nuclear morphology modification, and deficient receptor signaling. The mutations also impaired collective cell migration but enhanced cell-autonomous motility in the presence of Lphn3. Overall, these findings provide important insights into the cellular and molecular events linking Lphn3 genetic somatic mutations to cancer-related pathogenesis mechanisms.
Review
Biochemistry & Molecular Biology
Axel T. Brunger, Jeremy Leitz
Summary: Synaptic neurotransmitter release involves a complex interplay of presynaptic proteins, including SNAREs, synaptotagmin, complexin, and other factors. This review focuses on the interactions between the SNARE complex and synaptotagmin, particularly the validated primary interface. The study also discusses other potential interfaces and presents new data on the tripartite interface and an inhibitor of the primary interface in a reconstituted system of synaptic vesicle fusion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Kailu Yang, Chuchu Wang, Alex J. B. Kreutzberger, Ravi Ojha, Suvi Kuivanen, Sergio Couoh-Cardel, Serena Muratcioglu, Timothy J. Eisen, K. Ian White, Richard G. Held, Subu Subramanian, Kendra Marcus, Richard A. Pfuetzner, Luis Esquivies, Catherine A. Doyle, John Kuriyan, Olli Vapalahti, Giuseppe Balistreri, Tom Kirchhausen, Axel T. Brunger
Summary: A newly designed extended HR2 peptide has been shown to effectively inhibit the infection of SARS-CoV-2 and its variants, demonstrating a higher antiviral efficacy. This finding may provide new insights for the development of novel therapeutic drugs targeting SARS-CoV-2 and other related viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Klaudia Jaczynska, Luis Esquivies, Richard A. Pfuetzner, Baris Alten, Kyle D. Brewer, Qiangjun Zhou, Ege T. Kavalali, Axel T. Brunger, Josep Rizo
Summary: Characterizing the interactions between Synaptotagmin-1 and the SNARE complex is critical for understanding neurotransmitter release. This study investigates the binding of Synaptotagmin-1 to the SNARE complex through two interfaces, the primary interface and the tripartite interface. The results suggest the need for further research methods to accurately determine the binding mechanism.
Article
Multidisciplinary Sciences
Kailu Yang, Chuchu Wang, Alex J. B. Kreutzberger, K. Ian White, Richard A. Pfuetzner, Luis Esquivies, Tomas Kirchhausen, Axel T. Brunger
Summary: The Omicron variant of SARS-CoV-2 introduced several mutations, including N969K in the highly conserved HR1 region critical for membrane fusion. This mutation leads to structural changes in the HR2 backbone and reduces the efficacy of fusion-entry peptide inhibitors based on the Wuhan strain. A new peptide inhibitor specifically designed for Omicron shows restored inhibition activity and suggests a potential strategy to combat future variants. Mechanistically, our findings highlight the importance of interactions in the extended HR2 region during the transition of the S protein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Yan Gao, Yousuf A. Khan, Weike Mo, K. Ian White, Matthew Perkins, Richard A. Pfuetzner, Josef G. Trapani, Axel T. Brunger, Teresa Nicolson
Summary: The AAA+ NSF complex plays a crucial role in disassembling SNARE complexes before and after membrane fusion. Dysfunction of NSF can lead to serious developmental and degenerative defects. In our study using zebrafish, we identified a mutation in nsf, I209N, which specifically impairs hearing and balance without affecting other aspects such as motility, myelination, and innervation. In vitro experiments showed that the effects of I209N NSF protein on disassembling SNARE complexes vary depending on the type and concentration of the complexes. This study suggests that the selective effects on NSF-mediated membrane trafficking and auditory/vestibular function result from the differential disassembly of SNARE complexes.
Article
Pharmacology & Pharmacy
Estefania Y. Ojeda-Muniz, Brenda Rodriguez-Hernandez, Kerlys G. Correoso-Brana, Petra L. Segura-Landa, Antony A. Boucard
Summary: Adhesion G protein-coupled receptors (aGPCRs) possess a unique topology with a GPCR proteolysis site (GPS) that generates functionally distinct fragments upon autoproteolysis. The function of GPS cleavage has been enigmatic, but this study reveals that cleavage deficiency leads to biased signalling in aGPCRs. Specifically, cleavage-deficient ADGRL3 exhibits constitutive activity and shows a signalling bias towards select G proteins.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)