Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms23169101
Keywords
chromaffin cells; exocytosis; alpha 3 beta 4 acetylcholine nicotinic receptor; SNAP-25; DBH; secretory machinery; particle-based methods; modeling of calcium dynamics
Funding
- Spanish Ministerio de Economia y Competitividad (MINECO, FEDER, UE) [PID2020-114824GB-I00]
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This study reveals the association of nAChRs with the secretory active zones in bovine chromaffin cells and demonstrates the dynamic behavior of these receptors during the secretory process. The findings suggest that the mobility of α3β4 nAChR clusters may enhance the efficiency of the secretory response in chromaffin cells.
The heteromeric assembly of alpha 3 and beta 4 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 alpha 3 beta 4 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 alpha 3 beta 4 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.
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