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Membrane composition influences the conformation and function of the dopamine transporter in vivo
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- SummaryThe biophysical and biochemical properties of membrane lipids can alter the conformation and function of membrane-spanning proteins, yet the specific, physiological consequence in vivo of changing the membrane milieu for a specific protein has been rarely investigated. Using various genetic approaches to eliminate expression of the membrane-associated protein Flotillin-1, we have found that the lipid environment of the dopamine transporter (DAT) is necessary for mice to respond to amphetamine but not cocaine, because the localization of DAT to cholesterol-rich membranes is required for a DAT conformation that is essential for reverse transport of dopamine. Furthermore, a conditional rather than constitutive loss-of-function approach was necessary to reveal this phenotype, indicating a broader role for membrane-protein interactions that are modulated by Flotillin-1. Taken together, these findings demonstrate how interaction of a transmembrane protein with its membrane environment can regulate distinct events in the vertebrate brain that give rise to specific behavioral outcomes.
- Subjects :
- 0303 health sciences
biology
Chemistry
Membrane lipids
food and beverages
Transmembrane protein
Cell biology
03 medical and health sciences
0302 clinical medicine
Membrane
In vivo
Dopamine
biology.protein
medicine
Amphetamine
030217 neurology & neurosurgery
Function (biology)
030304 developmental biology
Dopamine transporter
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c5cc72a2e38cd7f44e5217a56812ad81
- Full Text :
- https://doi.org/10.1101/755819