Quantum dots reveal heterogeneous membrane diffusivity and dynamic surface density polarization of dopamine transporter
| Autor: | Sandra J. Rosenthal, Riley S. Ferguson, Ian D. Tomlinson, Oleg Kovtun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Dopamine Cell Mutant Cell Membranes Biochemistry Reuptake 0302 clinical medicine Catecholamines Amines Cytoskeleton Mass Diffusivity Multidisciplinary biology Chemistry Organic Compounds Physics Neurochemistry Neurotransmitters Lipids medicine.anatomical_structure Membrane Cholesterol Physical Sciences Medicine Cellular Structures and Organelles Algorithms medicine.drug Research Article Cell Physiology Biogenic Amines Science 03 medical and health sciences Structure-Activity Relationship Quantum Dots parasitic diseases mental disorders medicine Animals Humans Dopamine transporter Dopamine Transporters Dopamine Plasma Membrane Transport Proteins Chemical Physics Cell Membrane Organic Chemistry Chemical Compounds Reproducibility of Results Biology and Life Sciences Membrane Proteins Proteins Cell Biology Models Theoretical Hormones 030104 developmental biology HEK293 Cells nervous system Quantum dot Membrane Trafficking biology.protein Biophysics Heterologous expression 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE, Vol 14, Iss 11, p e0225339 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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