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

Cremona ML, Matthies HJ, Pau K, Bowton E, Speed N, Lute BJ, Anderson M, Sen N, Robertson SD, Vaughan RA, Rothman JE, Galli A, Javitch JA, Yamamoto A
Nat Neurosci. 2011 14 (4): 469-77

PMID: 21399631 · PMCID: PMC3066276 · DOI:10.1038/nn.2781

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.

MeSH Terms (12)

Animals Dopamine Plasma Membrane Transport Proteins Endocytosis Excitatory Amino Acid Transporter 2 HEK293 Cells HeLa Cells Humans Membrane Microdomains Membrane Proteins Mice Neuroglia Protein Kinase C

Connections (1)

This publication is referenced by other Labnodes entities:

Links