Author:

Keywords:

C14/21/095#56286976, C14/17/063#54271136

Abstract:

Cells have developed a sophisticated sensing and signaling system to adapt and survive in response to a variety of environmental challenges, such as temperature, pH, osmotic pressure, and nutrient availability. As in other eukaryotes, yeast cells employ a complex Ca2+ signaling network to regulate diverse cellular processes upon external stimuli. Several lines of evidence indicate that the glucose-induced activation of plasma membrane H+-ATPase is dependent on cellular Ca2+ signaling, which reveals an intimate connection between pH and Ca2+ homeostasis. Dysregulated pH and Ca2+ homeostasis are both linked to numerous human diseases, including neurodegenerative disorders in Alzheimer's disease, Parkinson's disease, and inflammatory processes in multiple sclerosis as well as different types of cancer. However, the correlations between external pH, intracellular pH, and Ca2+ metabolism remain unclear. The elucidation of these pivotal cellular mechanisms may provide new opportunities for the development of novel disease therapies. To decipher the crosslinks between pH and Ca2+ homeostasis in yeast, three objectives were formulated in this research: 1). Dissect correlations between Ca2+ metabolism and intracellular pH regulation. 2). Elucidate the interplay between V-ATPase and Pma1 at different external pH. 3). Document the importance of pH and Ca2+ homeostasis in a humanized yeast model for synucleinopathy.