Dynamic control of the dopamine transporter in neurotransmission and homeostasis

Abstract The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevate...

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Autores principales:	Mengfei Bu, Matthew J. Farrer, Habibeh Khoshbouei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/86d8223a39674efcbce9a1f8c5a35aa6
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spelling	oai:doaj.org-article:86d8223a39674efcbce9a1f8c5a35aa62021-12-02T13:20:25ZDynamic control of the dopamine transporter in neurotransmission and homeostasis10.1038/s41531-021-00161-22373-8057https://doaj.org/article/86d8223a39674efcbce9a1f8c5a35aa62021-03-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00161-2https://doaj.org/toc/2373-8057Abstract The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevated in early symptomatic PD and in presymptomatic individuals with monogenic mutations causal for parkinsonism. As an integral plasma membrane protein, DAT surface expression is dynamically regulated through endocytic trafficking, enabling flexible control of dopamine signaling in time and space, which in turn critically modulates movement, motivation and learning behavior. Yet the cellular machinery and functional implications of DAT trafficking remain enigmatic. In this review we summarize mechanisms governing DAT trafficking under normal physiological conditions and discuss how PD-linked mutations may disturb DAT homeostasis. We highlight the complexity of DAT trafficking and reveal DAT dysregulation as a common theme in genetic models of parkinsonism.Mengfei BuMatthew J. FarrerHabibeh KhoshboueiNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Mengfei Bu Matthew J. Farrer Habibeh Khoshbouei Dynamic control of the dopamine transporter in neurotransmission and homeostasis
description	Abstract The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevated in early symptomatic PD and in presymptomatic individuals with monogenic mutations causal for parkinsonism. As an integral plasma membrane protein, DAT surface expression is dynamically regulated through endocytic trafficking, enabling flexible control of dopamine signaling in time and space, which in turn critically modulates movement, motivation and learning behavior. Yet the cellular machinery and functional implications of DAT trafficking remain enigmatic. In this review we summarize mechanisms governing DAT trafficking under normal physiological conditions and discuss how PD-linked mutations may disturb DAT homeostasis. We highlight the complexity of DAT trafficking and reveal DAT dysregulation as a common theme in genetic models of parkinsonism.
format	article
author	Mengfei Bu Matthew J. Farrer Habibeh Khoshbouei
author_facet	Mengfei Bu Matthew J. Farrer Habibeh Khoshbouei
author_sort	Mengfei Bu
title	Dynamic control of the dopamine transporter in neurotransmission and homeostasis
title_short	Dynamic control of the dopamine transporter in neurotransmission and homeostasis
title_full	Dynamic control of the dopamine transporter in neurotransmission and homeostasis
title_fullStr	Dynamic control of the dopamine transporter in neurotransmission and homeostasis
title_full_unstemmed	Dynamic control of the dopamine transporter in neurotransmission and homeostasis
title_sort	dynamic control of the dopamine transporter in neurotransmission and homeostasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/86d8223a39674efcbce9a1f8c5a35aa6
work_keys_str_mv	AT mengfeibu dynamiccontrolofthedopaminetransporterinneurotransmissionandhomeostasis AT matthewjfarrer dynamiccontrolofthedopaminetransporterinneurotransmissionandhomeostasis AT habibehkhoshbouei dynamiccontrolofthedopaminetransporterinneurotransmissionandhomeostasis
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Dynamic control of the dopamine transporter in neurotransmission and homeostasis

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