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Sortilin and L-type Calcium Channels May be Involved in the Unusual Mechanism of proBDNF Signaling in Regenerating Mouse Neuromuscular Junctions
Neurochemical Research. 2025. Vol. 50. Article 104.
proBDNF and its main proteolytic product BDNF play crucial roles in maturation of neuromuscular junctions during development or reinnervation. We investigated the mechanisms of acute proBDNF effects on synaptic transmission in mouse motor synapses regenerating after nerve crush. The cleavage-resistant proBDNF mimicked the previously shown effect of cleavable proBDNF– GIRK-mediated decrease in the miniature endplate potential (MEPP) frequency accompanied by slight hyperpolarization of postsynaptic membrane. Remarkably, this effect did not utilize canonical proBDNF signaling pathway since inhibition of either p75 receptors with LM11A-31 or sortilin with AF38469 was not able to prevent it. Without sortilin activity, proBDNF downregulated the quantal content of multiquantal endplate potentials (EPP). This non-canonical action of proneurotrophin via TrkB receptors highlights the important role of sortilin as a safeguard preventing the spread of the negative effect of proBDNF on the evoked neurotransmitter release in regenerating motor synapses. In the absence of sortilin activity L-type calcium channels emerged as the key players providing proBDNF-induced decrease of EPP quantal content, while they were not involved in proBDNF-induced decrease of MEPP frequency. Sortilin-independent but TrkB- and GIRK-mediated inhibition of spontaneous release by proBDNF was not associated with the activity of acetylcholine (M2) or purinergic (A1 and P2Y13) metabotropic receptors. We propose that depending on sortilin involvement, proBDNF selectively affects spontaneous or evoked quantal neurotransmitter release via different branches of signaling pathway that ensure the presynaptic activation of GIRK or L-type calcium channels, respectively.
Nersisyan A., Frontiers in Molecular Biosciences 2026 Vol. 13 Article 1995001
Antiviral activity is commonly summarized using endpoint measures such as EC50 or EC90, yet these quantities emerge from a dynamic biological system and depend on viral replication kinetics, host-cell properties, experimental design, and the assay used to quantify infection. Infectious-virus titers, viral RNA, infected-cell fractions, viability measurements, and immune readouts capture different components of the ...
Added: October 15, 2026
Тукачев Н. В., González-Jiménez M., Ramakrishnan G. et al., Physical Chemistry Chemical Physics 2021 Vol. 23 No. 23 P. 13250–13260
Low-frequency vibrations play an essential role in biomolecular processes involving DNA such as gene expression, charge transfer, drug intercalation, and DNA–protein recognition. However, understanding the vibrational basis of these mechanisms relies on theoretical models due to the lack of experimental evidence. Here we present the low-frequency vibrational spectra of G-quadruplexes (structures formed by four strands ...
Added: October 14, 2026
Батова О. Н., Савинецкая Л. Е., Проявка С. В. et al., Nature Conservation Research. Заповедная наука 2026 Т. 11 № 4 С. 25–39
Spermophilus suslicus is a threatened species listed in Red Data Books at all levels (from regional Red Data
Books to the IUCN Red List of Threatened Species), and it currently requires special conservation activity.
Over the past 30–50 years, its range has changed from continuous to mosaic, and its population has declined
everywhere. In 2015, in Russia experimental ...
Added: October 13, 2026
Temereva E., Zoologischer Anzeiger 2026 Vol. 325 P. 182–195
Brachiopoda is a group of animals, that is still insufficiently studied at the ultrastructural level, despite the significance of ultrastructure of tissues and organs for analysing the functional morphology, reconstructing the organisation and biology of numerous extinct brachiopods, and establishing relationships among major taxa. In the present study, we provide a revised reconstruction of the ...
Added: October 11, 2026
Ekaterina D. Riumina, Klink G. V., Alekseeva E. et al., PNAS, США 2026 Vol. 123 No. 35 P. 1–20
The role of escape from the cytotoxic T cell (CTL) response in SARS-CoV-2 evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the HLA class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and ...
Added: October 2, 2026
Aly Ismailov, Poptsova M., Plos One 2026 Vol. 21 No. 9 Article e0355902
Added: October 2, 2026
Knyazev E., Чеботарева О. Е., М.: Издательский дом НИУ ВШЭ, 2026.
This teaching and learning guide provides a concise overview of the theoretical and practical aspects of the basic skills required to work in a biological laboratory. It also includes protocols for practical classes conducted as part of the introductory professional training placement for first-year students in the Bachelor’s programme in Cell and Molecular Biotechnology at ...
Added: September 30, 2026
Ryskina H., Knyazev E., Вопросы биологической, медицинской и фармацевтической химии 2026 Т. 29 № 9 С. 84–91
Introduction. The active integration of rapidly developing omics and computer technologies in the 21st century has led to a breakthrough in understanding the principles of the functioning of living systems. One of the dynamically developing integrative areas in biology is biological modeling. The fundamental paradigm has been the methodology that allows for the prediction of ...
Added: September 29, 2026
Lin Z., Duan K., Wan R. et al., Advanced Science 2026 P. 1–13
Targeted protein degradation represents a promising therapeutic strategy, yet its broader application is often limited by the scarcity of usable E3 ligases. Glutathione peroxidase 4 (GPX4) is a key target for inducing ferroptosis, but achieving sustained and potent inhibition remains challenging with conventional enzymatic inhibitors. Herein, we report the first small‐molecule GPX4 degraders that incorporate ...
Added: September 26, 2026
Diachkova E., Nikulin D., Кубкин Я. В. et al., American Journal of Respiratory and Critical Care Medicine 2026 Vol. 212
Accurate classification of a patient with pulmonary hypertension (PH) into one of five groups is fundamental for appropriate disease management strategies. The time from disease onset to correct diagnosis is unacceptably long in many cases. Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a consequence of venous thromboemboli, resulting in a more pronounced hereditary predisposition to ...
Added: September 23, 2026
Xu Y., Ryabov F., Alexandrov I. et al., USA 2026 Vol. 6 No. 8 Article 101324
Центромеры обеспечивают расхождение хромосом, однако организацию их хроматина в пределах повторяющейся альфа-сателлитной ДНК долгое время было трудно изучать. Для решения этой задачи мы создали гаплотип-разрешённые аннотации сателлитной ДНК для полной диплоидной сборки генома человека T2T-HG002. Затем с помощью метода направленного метилирования с секвенированием длинных прочтений (DiMeLo-seq) мы картировали центромерный белок A (CENP-A), модификацию H3K9me3 и ...
Added: September 23, 2026
Hebbar P., Ryabov F., Alexandrov I. et al., Cell 2026 Vol. 189 P. 4891–4908.e12
The common marmoset is a New World monkey widely used to study primate evolution and human disease. We present a telomere-to-telomere (T2T) reference assembly for the species, plus three near-T2T haplotypes. These resolve previously inaccessible regions, including the centromeres, sex chromosomes, subterminal satellites, acrocentric chromosomes, and the major histocompatibility complex (MHC). We find marmoset centromeres ...
Added: September 23, 2026
Shaitan A., Ke Y., Shutao C. et al., 2026 No. 24 Article 181
Background Therapeutic peptides exert pivotal effects in diverse biological processes, and have attracted significant interest in the field of biomedicine in recent years. However, most existing methods often fail to adequately capture the intricate interactions among amino acid residues and the contextual dependencies within peptide sequences, which hampers the extraction of deep semantic representations and ...
Added: September 18, 2026
Anton Rogachev, Sysoeva O., Frontiers in Systems Neuroscience 2025 Vol. 19 Article 1658243
Added: September 17, 2026
Anton Rogachev, Sysoeva O., Cognitive Systems Research 2024 Vol. 86 Article 101236
Receptive speech is the ability to understand speech addressed to a person. It is a crucial process for a child’s cognitive development. We examine the relationship between receptive speech and neural tracking of natural speech in 52 children aged 3–8 years to infer the neurophysiological mechanisms underlying speech development. We registered a 32-channel electroencephalogram (EEG) ...
Added: September 17, 2026
Чеботарева О. Е., Пирогов А. А., Antipenko I. et al., Доклады российской академии наук. Науки о жизни 2026 Т. 529 № 1 С. 389–395
Preeclampsia (PE) is a severe obstetric complication caused by chronic placental ischaemia. Genome-wide profiling of microRNA isoforms in two trophoblast hypoxia models (CoCl2 and the oxyquinoline derivative neuradapt, BeWo b30 cells) and clinical PE samples (placental tissue, syncytiotrophoblast vesicles) revealed concordant downregulation of hsa-miR-143-3p isoforms. Under a strict fold-change threshold, the canonical isoform (21 nt) ...
Added: September 16, 2026
Boldyreva M., Zubkova E., Trubkina E. et al., Frontiers in Cell and Developmental Biology 2025 No. 13 Article 1603405
Over the past two decades, interest in spiny mice (Acomys species) has increased significantly, as they represent a unique model for experimental work (Gaire et al., 2021; Sandoval et al., 2020). In the process of evolution, Acomys sp. have retained an amazing ability to regeneration of various body tissues in adulthood. A number of studies ...
Added: July 16, 2025
Bogacheva P., Molchanova A., Pravdivceva E. et al., Frontiers in Cellular Neuroscience 2022 Vol. 16 Article 866802
The effects of brain-derived neurotrophic factor (BDNF) processing by-products (proBDNF and BDNF prodomain) on the activity of mouse neuromuscular junctions (NMJs) were studied in synapses formed during the reinnervation of extensor digitorum longus muscle (m. EDL) and mature synapses of the diaphragm. The parameters of spontaneous miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) ...
Added: March 21, 2025
Kuzmin V. S., Egorov Y. V., Karhov A. M. et al., Doklady Biological Sciences 2025 Vol. 520 P. 73–79
Spiny mice (Acomys cahirinus) exhibit the ability to regenerate the damaged myocardium and functionalindices of the heart. demonstrated in various models of cardiac pathologies. Cardioregenerative potentialof Acomys is associated with partial preservation of the neonatal phenotype of cardiac tissue in adult animals.The electrophysiology and mechanisms regulating the heart rhythm in Acomys are extremely poorlyunderstood. The ...
Added: February 26, 2025
Gaydukov A., Balezina O., Brain and Behavior 2018 Vol. 8 No. 8 Article e01058
OBJECTIVE: The aim of this study was to identify the mechanism responsible for an increase in miniature endplate potentials (MEPPs) amplitude, induced by ryanodine as an agonist of ryanodine receptors in mouse motor nerve terminals. METHODS: Using intracellular microelectrode recordings of MEPPs and evoked endplate potentials (EPPs), the changes in spontaneous and evoked acetylcholine release ...
Added: June 26, 2021
Miteva A., Gaydukov A., Shestopalov V. et al., Purinergic Signalling 2018 Vol. 14 P. 459–469
P2X7 receptors are present in presynaptic membranes of motor synapses, but their regulatory role in modulation of neurotransmitter release remains poorly understood. P2X7 receptors may interact with pannexin 1 channels to form a purinergic signaling unit. The potential mechanism of P2X7 receptor-dependent modulation of acetylcholine (ACh) release was investigated by recording miniature endplate potentials (MEPPs) ...
Added: June 26, 2021
Tarasova E., Gaydukov A., Balezina O., Biochemistry. Biokhimiia 2018 Vol. 83 No. 6 P. 674–689
Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has ...
Added: June 26, 2021
Gaydukov A., Bogacheva P., Tarasova E. et al., Cells 2019 Vol. 8 No. 7 Article 762
The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recordings of MEPPs and EPPs were used to evaluate the changes in ...
Added: June 26, 2021
Tarasova E., Khotkina N., Gaydukov A. et al., Moscow University Biological Sciences Bulletin 2021 Vol. 76 No. 1 P. 1–6
Changes in the parameters of miniature endplate potential (MEPP) of mouse diaphragm caused by exogenous application of two classical endocannabinoids, 2-arachidonoylglycerol (2-AG) (1 μM) and anandamide (AEA) (30 μM), were compared. A slowly developing stable increase in the MEPP amplitude by 50%, without affecting the frequency of MEPPs, was caused by 2-AG. This effect was ...
Added: June 26, 2021