UBC Theses and Dissertations
PI4P pH-biosensing regulates Osh1-mediated lipid counter-transport Liu, Peter (Xiao Hu)
Phosphomonoester-containing phospholipids are an important group of signaling lipids with pKa values in the physiological range. The protonation state of phosphomonoester headgroups can respond linearly to the surrounding pH, allowing for pH-sensing. Previous work has established phosphatidic acid (PA) as a pH biosensor. A similar function exists for phosphatidylinositol 4-phosphate (PI4P) in its pH-dependent binding to the yeast oxysterol-binding protein (OSBP) homolog Osh1, an interaction which regulates the localization of the high affinity tryptophan permease Tat2. To solidify PI4P as a pH biosensor, an understanding of its pH-sensing in a physiological context is necessary. Using glucose as a physiological signal, we demonstrate that the interaction between PI4P and Osh1 is regulated by glucose in a pH-dependent manner. We provide evidence that Tat2 is regulated by glucose through pH, and that Osh1 regulation of Tat2 localization is likely through the lipid counter-transport activity of Osh1 at ER-trans-Golgi network (TGN) contact sites. Thus, we propose a model where pH-biosensing by PI4P in response to glucose availability regulates Tat2 sorting through lipid counter-transport by Osh1.
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