The dopamine membrane transporter plays an active modulatory role in synaptic dopamine homeostasis.
The dopamine membrane transporter plays an active modulatory role in synaptic dopamine homeostasis.
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DOI：
10.1002/jnr.24965
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发表时间：
2022-08
影响因子：
4.2
通讯作者：
Dhillon, Harbinder S.
中科院分区：
文献类型：
--
作者：
Formisano, Rosaria;Rosikon, Katarzyna D.;Singh, Abhyudai;Dhillon, Harbinder S.
关键词：
Modulatory mechanisms of neurotransmitter release and clearance are highly controlled processes whose finely-tuned regulation is critical for functioning of the nervous system. Dysregulation of the monoamine neurotransmitter dopamine can lead to several neuropathies. Synaptic modulation of dopamine is known to involve pre-synaptic D2 auto-receptors and acid sensing ion channels. In addition, the dopamine membrane transporter (DAT) which is responsible for clearance of dopamine from the synaptic cleft, is suspected to play an active role in modulating release of dopamine. Using functional imaging on the C. elegans model system, we show that DAT-1 acts as a negative feedback modulator to neurotransmitter vesicle fusion. Results from our fluorescence recovery after photo-bleaching (FRAP) based experiments were followed up with and reaffirmed using swimming-induced paralysis (SWIP) behavioral assays. Utilizing our numerical FRAP data we have developed a mechanistic model to dissect the dynamics of synaptic vesicle fusion, and compare the feedback effects of DAT-1 with the dopamine auto‐receptor. Our experimental results and the mechanistic model are of potential broader significance as similar dynamics are likely to be used by other synaptic modulators including membrane transporters for other neurotransmitters across species. The pH-sensitive fluorescent sensor remains OFF inside neurotransmitter vesicles due to low pH. Upon fusion of the vesicle with the synaptic membrane, the sensor is exposed to the neutral extra-cellular pH which switches it to the ON configuration. FRAP imaging of vesicle fusion dynamics reveals an active role for the dopamine membrane transporter in synaptic dopamine homeostasis.
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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作者：
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KENYON, CJ
DOI：
10.1101/lm.041830.116
发表时间：
2016-10
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
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Rankin CH
DOI：
10.1534/g3.112.003533
发表时间：
2012-08
期刊：
G3 (Bethesda, Md.)
影响因子：
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通讯作者：
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DOI：
10.1534/g3.114.010819
发表时间：
2014-04-07
期刊：
G3 (Bethesda, Md.)
影响因子：
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Felton CM;Johnson CM
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