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• W2797336150 abstract "Clathrin-independent endocytosis (CIE) mediates internalization of many transmembrane proteins but the mechanisms of cargo recruitment during CIE are poorly understood. We found that the cell-permeable furopyrimidine AIM-100 promotes dramatic oligomerization, clustering and CIE of human and mouse dopamine transporters (DAT), but not of their close homologues, norepinephrine and serotonin transporters. All effects of AIM-100 on DAT and the occupancy of substrate binding sites in the transporter were mutually exclusive, suggesting that AIM-100 may act by binding to DAT. Surprisingly, AIM-100-induced DAT endocytosis was independent of dynamin, cholesterol-rich microdomains and actin cytoskeleton, implying that a novel endocytic mechanism is involved. AIM-100 stimulated trafficking of internalized DAT was also unusual: DAT accumulated in early endosomes without significant recycling or degradation. We propose that AIM-100 augments DAT oligomerization through an allosteric mechanism associated with the DAT conformational state, and that oligomerization-triggered clustering leads to a coat-independent endocytosis and subsequent endosomal retention of DAT." @default.
• W2797336150 created "2018-04-24" @default.
• W2797336150 creator A5008628605 @default.
• W2797336150 creator A5033899179 @default.
• W2797336150 creator A5073726679 @default.
• W2797336150 creator A5076006747 @default.
• W2797336150 creator A5088924932 @default.
• W2797336150 date "2018-04-09" @default.
• W2797336150 modified "2023-09-27" @default.
• W2797336150 title "Small molecule induced oligomerization, clustering and clathrin-independent endocytosis of the dopamine transporter" @default.
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• W2797336150 doi "https://doi.org/10.7554/elife.32293" @default.
• W2797336150 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5896956" @default.

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