Single-quantum-dot tracking reveals altered membrane dynamics of an attention-deficit/hyperactivity-disorder-derived dopamine transporter coding variant

ACS Chemical Neuroscience
Oleg KovtunSandra J Rosenthal

Abstract

The presynaptic, cocaine- and amphetamine-sensitive dopamine (DA) transporter (DAT, SLC6A3) controls the intensity and duration of synaptic dopamine signals by rapid clearance of DA back into presynaptic nerve terminals. Abnormalities in DAT-mediated DA clearance have been linked to a variety of neuropsychiatric disorders, including addiction, autism, and attention deficit/hyperactivity disorder (ADHD). Membrane trafficking of DAT appears to be an important, albeit incompletely understood, post-translational regulatory mechanism; its dysregulation has been recently proposed as a potential risk determinant of these disorders. In this study, we demonstrate a link between an ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT transporter cell surface dynamics, a combination only previously studied with ensemble biochemical and optical approaches that featured limited spatiotemporal resolution. Here, we utilize high-affinity, DAT-specific antagonist-conjugated quantum dot (QD) probes to establish the dynamic mobility of wild-type and mutant DATs at the plasma membrane of living cells. Single DAT-QD complex trajectory analysis revealed that the DAT 615C variant exhibited increased membrane mobility relative to DAT 6...Continue Reading

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Citations

Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sijia WuHaley E Melikian
Apr 7, 2016·Neuroscience and Biobehavioral Reviews·Jameson PatakStephen V Faraone
Aug 21, 2015·PloS One·Scott M VanderwerfKim A Neve
Oct 20, 2017·Journal of Speech, Language, and Hearing Research : JSLHR·Naveen K Nagaraj
Mar 7, 2020·The Journal of Biological Chemistry·Rita R FaganHaley E Melikian
Dec 4, 2019·Biomaterials Science·Lucas B ThalSandra J Rosenthal
Jan 30, 2021·The Journal of Biological Chemistry·Rita R FaganHaley E Melikian
May 1, 2021·Frontiers in Cellular Neuroscience·Renae M RyanAnnalisa Scimemi
Sep 15, 2020·ACS Chemical Neuroscience·Daryl A GuthrieAmy Hauck Newman
Oct 16, 2021·Molecular Psychiatry·Maarten E A ReithZhicheng Lin
Oct 29, 2021·Cellular and Molecular Life Sciences : CMLS·Dolores PiniellaFrancisco Zafra
Dec 7, 2021·Frontiers in Cellular Neuroscience·Ian D TomlinsonSandra J Rosenthal

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