Unitat d'Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Spain.
Cells. 2021 Jun 4;10(6):1384. doi: 10.3390/cells10061384.
During the development of the nervous system, synaptogenesis occurs in excess though only the appropriate connections consolidate. At the neuromuscular junction, competition between several motor nerve terminals results in the maturation of a single axon and the elimination of the others. The activity-dependent release of transmitter, cotransmitters, and neurotrophic factors allows the direct mutual influence between motor axon terminals through receptors such as presynaptic muscarinic ACh autoreceptors and the tropomyosin-related kinase B neurotrophin receptor. In previous studies, we investigated the synergistic and antagonistic relations between these receptors and their downstream coupling to PKA and PKC pathways and observed a metabotropic receptor-driven balance between PKA (stabilizes multinnervation) and PKC (promotes developmental axonal loss). However, how much does each kinase contribute in the developmental synapse elimination process? A detailed statistical analysis of the differences between the PKA and PKC effects in the synapse elimination could help to explore this point. The present short communication provides this analysis and results show that a similar level of PKA inhibition and PKC potentiation would be required during development to promote synapse loss.
在神经系统发育过程中，突触发生过剩，但只有适当的连接才能巩固。在神经肌肉接头处，几个运动神经末梢之间的竞争导致单个轴突的成熟和其他轴突的消除。递质、共递质和神经营养因子的活性依赖性释放允许通过受体（如突触前毒蕈碱 ACh 自身受体和原肌球蛋白相关激酶 B 神经营养因子受体）在运动轴突末端之间进行直接的相互影响。在以前的研究中，我们研究了这些受体之间的协同和拮抗关系及其下游与 PKA 和 PKC 途径的偶联，并观察到 PKA（稳定多神经支配）和 PKC（促进发育性轴突丢失）之间代谢型受体驱动的平衡。然而，每种激酶在发育性突触消除过程中贡献多少？对 PKA 和 PKC 效应在突触消除中的差异进行详细的统计分析可以帮助探讨这一点。本简短交流提供了这种分析，结果表明，在发育过程中需要类似水平的 PKA 抑制和 PKC 增强来促进突触丢失。
