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单胺转运体的寡聚化。

Oligomerization of Monoamine Transporters.

机构信息

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Department of Chemical and Biomolecular Engineering, Department of Bioengineering, Center for Biophysics and Quantitative Biology, Department of Plant Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

出版信息

Subcell Biochem. 2024;104:119-137. doi: 10.1007/978-3-031-58843-3_7.

Abstract

Transporters of the monoamine transporter (MAT) family regulate the uptake of important neurotransmitters like dopamine, serotonin, and norepinephrine. The MAT family functions using the electrochemical gradient of ions across the membrane and comprises three transporters, dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). MAT transporters have been observed to exist in monomeric states to higher-order oligomeric states. Structural features, allosteric modulation, and lipid environment regulate the oligomerization of MAT transporters. NET and SERT oligomerization are regulated by levels of PIP2 present in the membrane. The kink present in TM12 in the MAT family is crucial for dimer interface formation. Allosteric modulation in the dimer interface hinders dimer formation. Oligomerization also influences the transporters' function, trafficking, and regulation. This chapter will focus on recent studies on monoamine transporters and discuss the factors affecting their oligomerization and its impact on their function.

摘要

单胺转运体(MAT)家族的转运体调节多巴胺、血清素和去甲肾上腺素等重要神经递质的摄取。MAT 家族利用跨膜离子的电化学梯度发挥作用,包含三种转运体,即多巴胺转运体(DAT)、血清素转运体(SERT)和去甲肾上腺素转运体(NET)。已经观察到 MAT 转运体存在于单体状态到更高阶的寡聚状态。结构特征、变构调节和脂质环境调节 MAT 转运体的寡聚化。NET 和 SERT 的寡聚化受膜中存在的 PIP2 水平调节。MAT 家族中 TM12 中的拐点对于二聚体界面的形成至关重要。二聚体界面的变构调节阻碍二聚体的形成。寡聚化也会影响转运体的功能、运输和调节。本章将重点介绍单胺转运体的最新研究,并讨论影响其寡聚化的因素及其对其功能的影响。

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