Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT.
Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT.
复制标题
DOI：
10.1038/nn.2781
复制
发表时间：
2011-04
影响因子：
25
通讯作者：
Yamamoto, Ai
中科院分区：
文献类型：
--
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
血浆神经递质转运体(NTT)调节多巴胺(DA)和谷氨酸等神经递质在大脑突触释放后的水平。包括蛋白激酶C(PKC)激活在内的刺激可导致某些NTT的内化和神经递质清除能力的降低。我们发现，Flotillin-1/Reggie-2(Flot1)蛋白是两个不同NTT家族成员--DA转运体(DAT)和胶质谷氨酸转运体EAAT2-在PKC调控下内化所必需的，我们还在Flot1中发现了一个保守的丝氨酸残基，这是转运蛋白内化所必需的。进一步的分析表明，在稳定的细胞系中，Flot1还需要将DAT定位在质膜微区内，并且对于苯丙胺诱导的神经元DA的反向运输是必不可少的，但对DA摄取来说并不是必需的。总之，我们的发现为富含Flot1的膜微域在PKC触发的DAT内吞作用和苯丙胺的作用中发挥关键作用提供了证据。
Plasmalemmal neurotransmitter transporters (NTTs) regulate the level of neurotransmitters, such as dopamine (DA) and glutamate, following their release at brain synapses. Stimuli including protein kinase C (PKC) activation can lead to the internalization of some NTTs and a reduction in neurotransmitter clearance capacity. We find that the protein Flotillin-1/Reggie-2 (Flot1) is required for PKC-regulated internalization of members of two different NTT families, the DA transporter (DAT) and the glial glutamate transporter EAAT2, and we have identified a conserved serine residue in Flot1 that is essential for transporter internalization. Further analysis revealed that Flot1 is also required to localize DAT within plasma membrane microdomains in stable cell lines, and is essential for amphetamine-induced reverse transport of DA in neurons but not for DA uptake. In sum, our findings provide evidence for a critical role of Flot1-enriched membrane microdomains in PKC-triggered DAT endocytosis and the actions of amphetamine.
登录
查看更多内容
影响因子：
4.8
作者：
Butchbach, MER;Tian, GL;Lin, CLG
通讯作者：
Lin, CLG
影响因子：
3.5
作者：
Galbiati, F;Volonté, D;Lisanti, MP
通讯作者：
Lisanti, MP
影响因子：
21.3
作者：
Glebov, OO;Bright, NA;Nichols, BJ
通讯作者：
Nichols, BJ
影响因子：
2.9
作者：
Adkins, Erika M.;Samuvel, Devadoss J.;Gether, Ulrik
通讯作者：
Gether, Ulrik
影响因子：
4.2
作者：
Guillet, BA;Velly, LJ;Pisano, P
通讯作者：
Pisano, P