Jansen Eric J R, Scheenen Wim J J M, Hafmans Theo G M, Martens Gerard J M
Department of Molecular Animal Physiology, Donders Centre for Neuroscience, Faculty of Science, Radboud University, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands.
Biochim Biophys Acta. 2008 Dec;1783(12):2301-10. doi: 10.1016/j.bbamcr.2008.06.020. Epub 2008 Jul 8.
The vacuolar (H(+))-ATPase (V-ATPase) is crucial for multiple processes within the eukaryotic cell, including membrane transport and neurotransmitter secretion. How the V-ATPase is regulated, e.g. by an accessory subunit, remains elusive. Here we explored the role of the neuroendocrine V-ATPase accessory subunit Ac45 via its transgenic expression specifically in the Xenopus intermediate pituitary melanotrope cell model. The Ac45-transgene product did not affect the levels of the prohormone proopiomelanocortin nor of V-ATPase subunits, but rather caused an accumulation of the V-ATPase at the plasma membrane. Furthermore, a higher abundance of secretory granules, protrusions of the plasma membrane and an increased Ca(2+)-dependent secretion efficiency were observed in the Ac45-transgenic cells. We conclude that in neuroendocrine cells Ac45 guides the V-ATPase through the secretory pathway, thereby regulating the V-ATPase-mediated process of Ca(2+)-dependent peptide secretion.
液泡型（H⁺）-ATP酶（V-ATP酶）对于真核细胞内的多种过程至关重要，包括膜运输和神经递质分泌。V-ATP酶是如何被调控的，例如通过一个辅助亚基进行调控，目前仍不清楚。在此，我们通过在非洲爪蟾垂体中间叶黑素细胞模型中特异性转基因表达，探究了神经内分泌V-ATP酶辅助亚基Ac45的作用。Ac45转基因产物不影响阿黑皮素原激素水平，也不影响V-ATP酶亚基水平，而是导致V-ATP酶在质膜上积累。此外，在Ac45转基因细胞中观察到分泌颗粒丰度更高、质膜有突起以及Ca²⁺依赖性分泌效率增加。我们得出结论，在神经内分泌细胞中，Ac45引导V-ATP酶通过分泌途径，从而调控V-ATP酶介导的Ca²⁺依赖性肽分泌过程。
