DOPAMINE TRANSPORTER ENDOCYTIC DETERMINANTS: CARBOXY TERMINAL RESIDUES CRITICAL FOR BASAL AND PKC-STIMULATED INTERNALIZATION
| Autor: | Haley E. Melikian, Deanna M. Navaroli, Zachary H. Stevens, Ekaterina Boudanova |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Neurotransmitter transporter
media_common.quotation_subject Dopamine Endocytic cycle Endocytosis Transfection PC12 Cells Article Reuptake Cellular and Molecular Neuroscience Downregulation and upregulation parasitic diseases mental disorders Animals Biotinylation Internalization Molecular Biology Protein kinase C Protein Kinase C media_common Dopamine transporter Dopamine Plasma Membrane Transport Proteins Alanine biology food and beverages Cell Biology Molecular biology Cell biology Protein Structure Tertiary Rats nervous system biology.protein |
| Popis: | Dopamine (DA) reuptake terminates dopaminergic neurotransmission and is mediated by DA transporters (DATs). Acute protein kinase C (PKC) activation accelerates DAT internalization rates, thereby reducing DAT surface expression. Basal DAT endocytosis and PKC-stimulated DAT functional downregulation rely on residues within the 587-596 region, although whether PKC-induced DAT downregulation reflects transporter endocytosis mechanisms linked to those controlling basal endocytosis rates is unknown. Here, we define residues governing basal and PKC-stimulated DAT endocytosis. Alanine substituting DAT residues 587-590 1) abolished PKC stimulation of DAT endocytosis, and 2) markedly accelerated basal DAT internalization, comparable to that of wildtype DAT during PKC activation. Accelerated basal DAT internalization relied specifically on residues 588-590, which are highly conserved among SLC6 neurotransmitter transporters. Our results support a model whereby residues within the 587-590 stretch may serve as a locus for a PKC-sensitive braking mechanism that tempers basal DAT internalization rates. |
| Databáze: | OpenAIRE |
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