Instituto de Neurociencias, CSIC-Universidad Miguel Hernández, Ctra de Valencia S/N, Sant Joan d'Alacant, 03550 Alicante, Spain.
Departamento Ciencias Básicas, UAM Azcapotzalco, México City 00810, México.
Int J Mol Sci. 2022 Aug 14;23(16):9101. doi: 10.3390/ijms23169101.
The heteromeric assembly of α3 and β4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3β4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3β4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.
α3 和 β4 亚基组成的异源二聚体似乎介导了牛肾上腺嗜铬细胞的分泌反应。然而，关于这些烟碱型乙酰胆碱受体（nAChRs）在这个细胞模型中的分泌活跃区的定位信息尚不清楚。本研究首次提供证据表明，实际上，一部分 nAChRs 通过 F-肌动蛋白细胞骨架与囊泡胞吐机制成分相关，如 SNAP-25 标记所检测到的。此外，我们还证明，在受到刺激时，α3β4 nAChRs 与胞吐事件非常接近的概率增加了随机分布，从而证实了这些受体在分泌过程中的明显动态行为。对分泌动力学和分泌成分分布的建模支持这样一种观点，即α3β4 nAChR 簇的流动性可以帮助提高嗜铬细胞分泌反应的效率。我们的研究受到传统共聚焦显微镜的限制；在这个意义上，从使用超分辨率显微镜技术在不久的将来可能会增强我们的结论。
