Plasticity of PI4KIIIα interactions at the plasma membrane

Plasma membrane PI4P is an important direct regulator of many processes that occur at the plasma membrane and also a biosynthetic precursor of PI(4,5)P-2 and its downstream metabolites. The majority of this PI4P pool is synthesized by an evolutionarily conserved complex, which has as its core the PI 4-kinase PI4KIII alpha (Stt4 in yeast) and also comprises TTC7 (Ypp1 in yeast) and the peripheral plasma membrane protein EFR3. While EFR3 has been implicated in the recruitment of PI4KIII alpha via TTC7, the plasma membrane protein Sfk1 was also shown to participate in this targeting and activity in yeast. Here, we identify a member of the TMEM150 family as a functional homologue of Sfk1 in mammalian cells and demonstrate a role for this protein in the homeostatic regulation of PI(4,5)P-2 at the plasma membrane. We also show that the presence of TMEM150A strongly reduces the association of TTC7 with the EFR3-PI4KIII alpha complex, without impairing the localization of PI4KIII alpha at the plasma membrane. Collectively our results suggest a plasticity of the molecular interactions that control PI4KIII alpha localization and function.