Direct PIP(2) binding mediates stable oligomer formation of the serotonin transporter.
Direct PIP(2) binding mediates stable oligomer formation of the serotonin transporter.
复制标题
PIP（2）的直接结合介导5-羟色胺转运蛋白的稳定寡聚体形成。
DOI：
10.1038/ncomms14089
复制
发表时间：
2017-01-19
影响因子：
16.6
通讯作者：
Schütz GJ
中科院分区：
文献类型：
--
作者：
Anderluh A;Hofmaier T;Klotzsch E;Kudlacek O;Stockner T;Sitte HH;Schütz GJ
人类血清素转运蛋白（hSERT）介导从突触间隙摄取血清素，从而终止血清素信号传导。我们之前通过单分子显微镜发现SERT在活细胞质膜上形成不同化学计量的稳定高阶寡聚物。在这里，我们报告内质网（ER）膜上的 SERT 寡聚物组装遵循动态平衡过程，其特征是不同寡聚物之间亚基的快速交换，以及寡聚程度的浓度依赖性。然而，在运输到质膜后，SERT 化学计量是固定的。寡聚 SERT 复合物的稳定是通过与磷酸肌醇磷脂酰肌醇 4,5-二磷酸 (PIP2) 的直接结合介导的。观察到的寡聚物形成与寡聚物操作位点的空间解耦为细胞提供了独立于细胞表面蛋白质密度定义蛋白质四级结构的能力。人类血清素转运蛋白（SERT）介导神经递质的摄取以终止神经元信号传导。在这里，作者使用单分子成像来深入了解 SERT 寡聚化的分子起源及其在质膜上的预设化学计量。
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization. After trafficking to the plasma membrane, however, the SERT stoichiometry is fixed. Stabilization of the oligomeric SERT complexes is mediated by the direct binding to phosphoinositide phosphatidylinositol-4,5-biphosphate (PIP2). The observed spatial decoupling of oligomer formation from the site of oligomer operation provides cells with the ability to define protein quaternary structures independent of protein density at the cell surface. The human serotonin transporter (SERT) mediates the uptake of neurotransmitters to terminate neuronal signalling. Here the authors use single-molecule imaging to get insight into the molecular origin of SERT oligomerization and their pre-set stoichiometry at the plasma membrane.