Super-resolution microscopy reveals functional organization of dopamine transporters into cholesterol and neuronal activity-dependent nanodomains.
Super-resolution microscopy reveals functional organization of dopamine transporters into cholesterol and neuronal activity-dependent nanodomains.
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DOI：
10.1038/s41467-017-00790-3
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发表时间：
2017-09-29
影响因子：
16.6
通讯作者：
Gether U
中科院分区：
文献类型：
--
作者：
Rahbek-Clemmensen T;Lycas MD;Erlendsson S;Eriksen J;Apuschkin M;Vilhardt F;Jørgensen TN;Hansen FH;Gether U
多巴胺调节奖赏、认知和运动功能。通过介导细胞外多巴胺的快速再摄取，多巴胺转运蛋白对于多巴胺能神经传递的时空控制至关重要。在这里，我们使用超分辨率成像显示，多巴胺转运蛋白被动态隔离到突触前静脉曲张和多巴胺能神经元的神经元投射的质膜中的胆固醇依赖性纳米结构域。随机光学重建显微镜显示不规则的多巴胺转运蛋白纳米结构域（平均直径约70 nm），胆固醇消耗高度敏感。活体光活化定位显微镜显示活异源细胞中类似的多巴胺转运蛋白膜组织。在神经元中，双色dSTORM显示酪氨酸羟化酶和囊泡单胺转运蛋白-2明显位于多巴胺转运蛋白纳米结构域附近，但不重叠。多巴胺转运蛋白在纳米结构域中的分子组织通过NMDA型离子型谷氨酸受体的短期激活可逆地减少，这暗示多巴胺转运蛋白纳米结构域分布是响应兴奋性输入调节多巴胺能神经传递的潜在机制。多巴胺转运蛋白（DAT）在神经传递的调节中起着至关重要的作用。在这里，作者使用超分辨率成像来显示DAT聚集到胆固醇依赖性膜区域，这些区域由离子型谷氨酸受体激活可逆地调节。
Dopamine regulates reward, cognition, and locomotor functions. By mediating rapid reuptake of extracellular dopamine, the dopamine transporter is critical for spatiotemporal control of dopaminergic neurotransmission. Here, we use super-resolution imaging to show that the dopamine transporter is dynamically sequestrated into cholesterol-dependent nanodomains in the plasma membrane of presynaptic varicosities and neuronal projections of dopaminergic neurons. Stochastic optical reconstruction microscopy reveals irregular dopamine transporter nanodomains (∼70 nm mean diameter) that were highly sensitive to cholesterol depletion. Live photoactivated localization microscopy shows a similar dopamine transporter membrane organization in live heterologous cells. In neurons, dual-color dSTORM shows that tyrosine hydroxylase and vesicular monoamine transporter-2 are distinctively localized adjacent to, but not overlapping with, the dopamine transporter nanodomains. The molecular organization of the dopamine transporter in nanodomains is reversibly reduced by short-term activation of NMDA-type ionotropic glutamate receptors, implicating dopamine transporter nanodomain distribution as a potential mechanism to modulate dopaminergic neurotransmission in response to excitatory input. The dopamine transporter (DAT) has a crucial role in the regulation of neurotransmission. Here, the authors use super-resolution imaging to show that DAT clusters into cholesterol-dependent membrane regions that are reversibly regulated by ionotropic glutamate receptors activation.
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影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
3.7
作者：
Blom H;Rönnlund D;Scott L;Westin L;Widengren J;Aperia A;Brismar H
通讯作者：
Brismar H
影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
DOI：
10.1073/pnas.0500489102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Habuchi, S;Ando, R;Hofkens, J
通讯作者：
Hofkens, J
影响因子：
25
作者：
Cremona, M. Laura;Matthies, Heinrich J. G.;Pau, Kelvin;Bowton, Erica;Speed, Nicole;Lute, Brandon J.;Anderson, Monique;Sen, Namita;Robertson, Sabrina D.;Vaughan, Roxanne A.;Rothman, James E.;Galli, Aurelio;Javitch, Jonathan A.;Yamamoto, Ai
通讯作者：
Yamamoto, Ai