The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein
The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein
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DOI：
10.1038/ncomms4101
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发表时间：
2014-01-01
影响因子：
16.6
通讯作者：
Marini, Anna Maria
中科院分区：
文献类型：
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作者：
Boeckstaens, Melanie;Llinares, Elisa;Marini, Anna Maria
TORC1复合物通过整合包括氨基酸可用性在内的营养信号来控制细胞生长。TORC1通过调节抑制蛋白介导的氨基酸转运蛋白内吞作用来调节质膜蛋白含量。在这里，我们证明了TORC1进一步微调氨转运蛋白Mep2的固有活性，Mep2是哺乳动物恒河猴因子的酵母同源物，独立于抑制素介导的内噬作用。TORC1效应激酶Npr1和上游TORC1调节因子Npr2通过磷酸化沉默一个羧基末端的自抑制结构域来控制Mep2的转运活性。在氮供应不足的情况下，Npr1使Mep2 S457磷酸化，从而提高铵转运活性。补充首选氮源谷氨酰胺可通过质膜Psr1和Psr2冗余磷酸酶导致Mep2失活和S457即刻去磷酸化。本研究强调，TORC1还可以调节营养物质的通透性，以快速灵活地响应环境扰动来调节细胞生长，从而在质膜上建立起降解、失活或维持活性的转运蛋白等级。
The TORC1 complex controls cell growth upon integrating nutritional signals including amino-acid availability. TORC1 notably adapts the plasma membrane protein content by regulating arrestin-mediated endocytosis of amino-acid transporters. Here we demonstrate that TORC1 further fine tunes the inherent activity of the ammonium transport protein, Mep2, a yeast homologue of mammalian Rhesus factors, independently of arrestin-mediated endocytosis. The TORC1 effector kinase Npr1 and the upstream TORC1 regulator Npr2 control Mep2 transport activity by phospho-silencing a carboxy-terminal autoinhibitory domain. Under poor nitrogen supply, Npr1 enables Mep2 S457 phosphorylation and thus ammonium transport activity. Supplementation of the preferred nitrogen source glutamine leads to Mep2 inactivation and instant S457 dephosphorylation via plasma membrane Psr1 and Psr2 redundant phosphatases. This study underscores that TORC1 also adjusts nutrient permeability to regulate cell growth in a fast and flexible response to environmental perturbation, establishing a hierarchy in the transporters to be degraded, inactivated or maintained active at the plasma membrane.