Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT
| Autor: | Ai Yamamoto, Sabrina D. Robertson, Aurelio Galli, Jonathan A. Javitch, Nicole Speed, M. Laura Cremona, Brandon J Lute, Kelvin Pau, Namita Sen, Monique Anderson, Erica Bowton, Roxanne A. Vaughan, James E. Rothman, Heinrich J.G. Matthies |
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| Rok vydání: | 2011 |
| Předmět: |
Dopamine Plasma Membrane Transport Proteins
media_common.quotation_subject Endocytosis Article Mice 03 medical and health sciences Membrane Microdomains 0302 clinical medicine Dopamine medicine Animals Humans Internalization Protein Kinase C 030304 developmental biology media_common Dopamine transporter Cocaine binding 0303 health sciences biology General Neuroscience Lipid microdomain Membrane Proteins Cell biology HEK293 Cells Excitatory Amino Acid Transporter 2 nervous system Membrane protein biology.protein Neuroglia Neuroscience 030217 neurology & neurosurgery HeLa Cells medicine.drug |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | Plasmalemmal neurotransmitter transporters (NTTs) regulate the level of neurotransmitters, such as dopamine (DA) and glutamate, after their release at brain synapses. Stimuli including protein kinase C (PKC) activation can lead to the internalization of some NTTs and a reduction in neurotransmitter clearance capacity. We found that the protein Flotillin-1 (Flot1), also known as Reggie-2, was required for PKC-regulated internalization of members of two different NTT families, the DA transporter (DAT) and the glial glutamate transporter EAAT2, and we identified a conserved serine residue in Flot1 that is essential for transporter internalization. Further analysis revealed that Flot1 was also required to localize DAT within plasma membrane microdomains in stable cell lines, and was essential for amphetamine-induced reverse transport of DA in neurons but not for DA uptake. In sum, our findings provide evidence for a critical role of Flot1-enriched membrane microdomains in PKC-triggered DAT endocytosis and the actions of amphetamine. |
| Databáze: | OpenAIRE |
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