Plasticity of PI4KIIIα interactions at the plasma membrane.

Plasticity of PI4KIIIα interactions at the plasma membrane.
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DOI:
10.15252/embr.201439151
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发表时间:
2015-03
期刊:
影响因子:
7.7
通讯作者:
De Camilli P
De Camilli P
中科院分区:
生物学2区
文献类型:
--
作者:
Chung J;Nakatsu F;Baskin JM;De Camilli P

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质膜PI 4 P是发生在质膜上的许多过程的重要直接调节剂,也是PI(4,5)P2及其下游代谢物的生物合成前体。该PI 4P池的大部分由进化上保守的复合物合成,该复合物以PI 4-激酶PI 4KIII α(酵母中的Stt 4)为核心,还包含TTC 7(酵母中的Ypp 1)和外周质膜蛋白EFR 3。虽然EFR 3通过TTC 7参与了PI 4 KIII α的募集,但质膜蛋白Sfk 1也显示参与了酵母中的这种靶向和活性。在这里,我们确定了TMEM 150家族的成员作为Sfk 1在哺乳动物细胞中的功能同源物,并证明了这种蛋白质在PI(4,5)P2在质膜的稳态调节中的作用。我们还表明,TMEM 150 A的存在强烈降低了TTC 7与EFR 3-PI 4KIII α复合物的结合,而不损害PI 4KIII α在质膜上的定位。总的来说,我们的结果表明,控制PI 4KIII α定位和功能的分子相互作用的可塑性。
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.
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