Quantum dots reveal heterogeneous membrane diffusivity and dynamic surface density polarization of dopamine transporter

Autoři: Oleg Kovtun aff001;  Ian D. Tomlinson aff001;  Riley S. Ferguson aff001;  Sandra J. Rosenthal aff001
Působiště autorů: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, United States of America aff001;  Vanderbilt Institute of Nanoscale Science and Engineering, Vanderbilt University, Nashville, Tennessee, United States of America aff002;  Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America aff003;  Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, United States of America aff004;  Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, United States of America aff005;  Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225339


The presynaptic dopamine transporter mediates rapid reuptake of synaptic dopamine. Although cell surface DAT trafficking recently emerged as an important component of DAT regulation, it has not been systematically investigated. Here, we apply our single quantum dot (Qdot) tracking approach to monitor DAT plasma membrane dynamics in several heterologous expression cell hosts with nanometer localization accuracy. We demonstrate that Qdot-tagged DAT proteins exhibited highly heterogeneous membrane diffusivity dependent on the local membrane topography. We also show that Qdot-tagged DATs were localized away from the flat membrane regions and were dynamically retained in the membrane protrusions and cell edges for the duration of imaging. Single quantum dot tracking of wildtype DAT and its conformation-defective coding variants (R60A and W63A) revealed a significantly accelerated rate of dysfunctional DAT membrane diffusion. We believe our results warrant an in-depth investigation as to whether compromised membrane dynamics is a common feature of brain disorder-derived DAT mutants.

Klíčová slova:

Cell membranes – Cytoskeleton – Dopamine – Cholesterol – Mass diffusivity – Membrane proteins – Membrane trafficking – Dopamine transporters


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Článek vyšel v časopise


2019 Číslo 11