Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Eric Jansen (Donders Series 75)

December 19, 2011.

Promotor: Prof.dr. G. Martens

New insights into V-ATPase functioning: the role of its accessory subunit Ac45 and a novel brain-specific Ac45 paralog

The V-ATPase is a multifunctional proton pump that determines the intraorganellar pH in a eukaryotic cell. It is however unclear how the pump is regulated. For the research described in his thesis, Eric Jansen generated transgenic neuroendocrine Xenopus melanotrope cells to identify an accessory subunit of the V-ATPase, the Ac45 protein, as a regulator of the pump. As such, the type I transmembrane protein Ac45 was found to be important for correct prohormone processing and Ca2+-dependent secretion. Moreover, a brain-specific variant of the Ac45 protein was discovered. This Ac45-variant was characterized and may play an important role in early mouse and rat brain development, more specifically in the process of neurite outgrowth of newly-born neuronal cells. Jansen hypothesizes that Ac45 and the Ac45-variant differentially guide the V-ATPase and thereby play important roles in cellular processes ranging from hormone release to neuronal outgrowth. Overall, the functional studies described in this thesis indicate that the genes encoding the Ac45 protein and the Ac45-variant represent interesting candidate genes for V-ATPase-related (neuronal) disorders.