Chung Jeeyun, Nakatsu Fubito, Baskin Jeremy M, De Camilli Pietro
Department of Cell Biology, Howard Hughes Medical Institute Program in Cellular Neuroscience, Neurodegeneration and Repair Yale University Medical School, New Haven, CT, USA.
Department of Cell Biology, Howard Hughes Medical Institute Program in Cellular Neuroscience, Neurodegeneration and Repair Yale University Medical School, New Haven, CT, USA
EMBO Rep. 2015 Mar;16(3):312-20. doi: 10.15252/embr.201439151. Epub 2015 Jan 21.
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)P2 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 PI4KIIIα (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 PI4KIIIα 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)P2 at the plasma membrane. We also show that the presence of TMEM150A strongly reduces the association of TTC7 with the EFR3-PI4KIIIα complex, without impairing the localization of PI4KIIIα at the plasma membrane. Collectively our results suggest a plasticity of the molecular interactions that control PI4KIIIα localization and function.
质膜磷脂酰肌醇-4-磷酸（PI4P）是许多发生在质膜上的过程的重要直接调节因子，也是磷脂酰肌醇-4,5-二磷酸（PI(4,5)P2）及其下游代谢产物的生物合成前体。大部分PI4P库是由一个进化上保守的复合物合成的，该复合物的核心是PI 4-激酶PI4KIIIα（酵母中的Stt4），还包括TTC7（酵母中的Ypp1）和外周质膜蛋白EFR3。虽然EFR3已被证明通过TTC7参与PI4KIIIα的募集，但质膜蛋白Sfk1在酵母中也参与了这种靶向和活性。在这里，我们鉴定出跨膜蛋白150（TMEM150）家族的一个成员是哺乳动物细胞中Sfk1的功能同源物，并证明该蛋白在质膜PI(4,5)P2的稳态调节中起作用。我们还表明，TMEM150A的存在强烈降低了TTC7与EFR3-PI4KIIIα复合物的结合，而不影响PI4KIIIα在质膜上的定位。我们的结果共同表明，控制PI4KIIIα定位和功能的分子相互作用具有可塑性。
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