Muscarinic Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Tomàs, Josep; Lanuza, María A.; Santafé, Manel M.; Cilleros-Mañé, Víctor; Just-Borràs, Laia; Balanyà-Segura, Marta; Полищук, А. А.; Nadal, Laura; Tomàs, Marta; García, Neus

doi:10.1007/s12035-022-03154-1

Cited by 3 publications

(7 citation statements)

References 99 publications

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“… Schematic representation of the localization of M2 and M4 subtypes muscarinic acetylcholine receptors and the associated signaling pathways in the neuromuscular synapse of vertebrates [ 7 , 8 , 29 , 48 , 52 , 58 ]; nAChR, nicotinic acetylcholine receptor; AC, adenylate cyclase; cAMP, cyclic adenosine monophosphate; PKC, protein kinase C; PKA, protein kinase A; A1/2A, adenosine receptor; PI3K/AKT/mTOR – the signaling pathway involving phosphatidylinositol 3-kinase, protein kinase B, and mTOR kinase …”

Section: Discussionmentioning

confidence: 99%

“… Schematic representation of the localization of M3 and M5 subtypes muscarinic acetylcholine receptors and the associated signaling pathways in the neuromuscular synapse of vertebrates [ 7 , 8 , 29 , 48 , 52 , 58 ]; nChR, nicotinic acetylcholine receptor, PLC, phospholipase C, DAG, diacylglycerol, IP3, inositol triphosphate, NO, nitric oxide, ENOS, endothelial form of NO synthase, EC, endocannabinoid (presumably 2-AG), CB, endocannabinoid receptor …”

Section: Discussionmentioning

confidence: 99%

“…It is assumed that M2 mAChR in the Schwann cells of warm-blooded animals is involved in the control of the proliferation, differentiation, and myelination of these cells [ 30 , 49 , 50 ]. In neuromuscular preparations of newborn rats, muscarinic autoreceptors of the M1, M2 and M4 subtypes can participate in the differentiation of “strong” and “weak” synapses in the case of polyinnervation of muscle fibers at early stages of synaptogenesis [ 51 , 52 ].…”

Section: Functional Role Of Machrs In Skeletal Musclementioning

confidence: 99%

“…Предполагается, что М2 мХР в шванновских клетках теплокровных участвует в контроле пролиферации, дифференцировки и миелинизации этих клеток [30,49,50]. В исследовании, выполненном на нервно-мышечных препаратах новорожденных крыс, было показано, что мускариновые ауторецепторы М1, М2 и М4 могут участвовать в дифференцировке «сильных» и «слабых» синапсов в случае полииннервации мышечных волокон на ранних стадиях синаптогенеза [51,52].…”

Section: функциональная роль мхр в скелетной мышцеunclassified

“…Нервное окончание [7,11,29]; сарколемма [8]; шванновская клетка [29] Увеличение квантового состава ПКП [10,11,29,31,63]; регуляция неквантовой секреции АХ и мембранного потенциала мышечного волокна [8,13,48]; дифференцировка «сильных» и «слабых» синапсов на ранних стадиях синаптогенеза [51,52] Активация фосфолипазы С, увеличение [Ca 2+ ] i , регулирование активности протеинкиназ А и С [52,58,63] М2 Нервное окончание, шванновская клетка [7,29,30,49,50] Ca 2+ -зависимая регуляция нейросекреции, квантового состава ПКП и временного хода секреции [11,29,34,43,44,65,66]; регуляция процессов пролиферации и дифференциации шванновских клеток [30,49,50]; контроль развития двигательных нервных окончаний в процессе онтогенеза [7], дифференцировка «сильных» и «слабых» синапсов на ранних стадиях синаптогенеза [51,52] Регулирование уровня сАМР и активности протеинкиназ А и С [52,58]; тонический блок аппарата экзоцитоза [66]; Ca 2+зависимая регуляция К + -канала (GIRK) и Ca 2+ -канала L-типа [65]; PI3K/AKT/mTOR-сигнальный путь [50] М3…”

Section: м1unclassified

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Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role

Kovyazina,

Khamidullina

2024

Acta Naturae

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The review focuses on the modern concepts of the functions of muscarinic cholinoreceptors in skeletal muscles, particularly, in neuromuscular contacts, and that of the signaling pathways associated with the activation of various subtypes of muscarinic receptors in the skeletal muscles of cold-blooded and warm-blooded animals. Despite the long history of research into the involvement of muscarinic receptors in the modulation of neuromuscular transmission, many aspects of such regulation and the associated intracellular mechanisms remain unclear. Now it is obvious that the functions of muscarinic receptors in skeletal muscle are not limited to the autoregulation of neurosecretion from motor nerve endings but also extend to the development and morphological rearrangements of the synaptic apparatus, coordinating them with the degree of activity. The review discusses various approaches to the study of the functions of muscarinic receptors in motor synapses, as well as the problems arising when interpreting experimental data. The final part of the review is devoted to an analysis of some of the intracellular mechanisms and signaling pathways that mediate the effects of muscarinic agents on neuromuscular transmission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Functional Role Of Machrs In Skeletal Musclementioning

confidence: 99%

Section: функциональная роль мхр в скелетной мышцеunclassified

Section: м1unclassified

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Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role

Kovyazina,

Khamidullina

2024

Acta Naturae

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Dendritic Spines: Synaptogenesis and Synaptic Pruning for the Developmental Organization of Brain Circuits

Petanjek,

Banovac,

Sedmak

et al. 2023

Advances in Neurobiology

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

Tomàs,

Cilleros-Mañé,

Just-Borràs

et al. 2023

Neural Regeneration Research

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During the development of the nervous system, there is an overproduction of neurons and synapses. Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening. We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway, at the neuromuscular junction, in the axonal development and synapse elimination process versus the synapse consolidation. The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination, in relation to other molecular pathways that we and others have found to regulate this process. In particular, we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors, coupled to downstream serine-threonine protein kinases A and C (PKA and PKC) and voltage-gated calcium channels, at different nerve endings in developmental competition. The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site, influence each other, and require careful studies to individualize the mechanisms of specific endings. We describe an activity-dependent balance (related to the extent of transmitter release) between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals. The downstream displacement of the PKA/PKC activity ratio to lower values, both in competing nerve terminals and at postsynaptic sites, plays a relevant role in controlling the elimination of supernumerary synapses. Finally, calcium entry through L- and P/Q- subtypes of voltage-gated calcium channels (both channels are present, together with the N-type channel in developing nerve terminals) contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination (the weakest in acetylcholine release and those that have already become silent). The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development. Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.

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Muscarinic Receptors in Developmental Axonal Competition at the Neuromuscular Junction

Cited by 3 publications

References 99 publications

Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role

Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role

Dendritic Spines: Synaptogenesis and Synaptic Pruning for the Developmental Organization of Brain Circuits

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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