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Nat Neurosci. 2011 Apr;14(4):469-77. doi: 10.1038/nn.2781. Epub 2011 Mar 13.

Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT.

Author information

1
Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.

Erratum in

  • Nat Neurosci. 2011 Dec;14(2):1617.

Abstract

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.

PMID:
21399631
PMCID:
PMC3066276
DOI:
10.1038/nn.2781
[Indexed for MEDLINE]
Free PMC Article

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