Laboratory of Molecular Neurochemistry, Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
PLoS One. 2013 Aug 13;8(8):e70872. doi: 10.1371/journal.pone.0070872. eCollection 2013.
Synaptic re-uptake of dopamine is dependent on the dopamine transporter (DAT), which is regulated by its distribution to the cell surface. DAT trafficking is modulated by the Parkinson's disease-linked protein alpha-synuclein, but the contribution of synuclein family members beta-synuclein and gamma-synuclein to DAT trafficking is not known. Here we use SH-SY5Y cells as a model of DAT trafficking to demonstrate that all three synucleins negatively regulate cell surface distribution of DAT. Under these conditions the synucleins limit export of DAT from the endoplasmic reticulum (ER) by impairment of the ER-Golgi transition, leading to accumulation of DAT in this compartment. This mechanism for regulating DAT export indirectly through effects on ER and Golgi function represents a previously unappreciated role for the extended synuclein family that is likely applicable to trafficking of the many proteins that rely on the secretory pathway.
多巴胺的突触再摄取依赖于多巴胺转运体（DAT），DAT 的分布决定其在细胞膜表面的表达水平。帕金森病相关蛋白α-突触核蛋白调节 DAT 的转运，但是β-突触核蛋白和γ-突触核蛋白是否参与 DAT 的转运尚不清楚。本文使用 SH-SY5Y 细胞作为 DAT 转运模型，证明三种突触核蛋白均负调控 DAT 在细胞膜表面的分布。在这些条件下，突触核蛋白通过损害内质网-高尔基体转运（ER-Golgi transition），限制 DAT 从内质网（ER）中的输出，导致 DAT 在这一区域聚集。这种通过影响 ER 和高尔基体功能间接调节 DAT 输出的机制，代表了对扩展突触核蛋白家族的一个新的认识，这可能适用于许多依赖分泌途径的蛋白的转运。
