Reference - Detail
| RRC ID | 74737 |
|---|---|
| Author | Shekar A, Mabry SJ, Cheng MH, Aguilar JI, Patel S, Zanella D, Saleeby DP, Zhu Y, Romanazzi T, Ulery-Reynolds P, Bahar I, Carter AM, Matthies HJG, Galli A. |
| Title | Syntaxin 1 Ser14 phosphorylation is required for nonvesicular dopamine release. |
| Journal | Sci Adv |
| Abstract |
Amphetamine (AMPH) is a psychostimulant that is commonly abused. The stimulant properties of AMPH are associated with its ability to increase dopamine (DA) neurotransmission. This increase is promoted by nonvesicular DA release mediated by reversal of DA transporter (DAT) function. Syntaxin 1 (Stx1) is a SNARE protein that is phosphorylated at Ser14 by casein kinase II. We show that Stx1 phosphorylation is critical for AMPH-induced nonvesicular DA release and, in Drosophila melanogaster, regulates the expression of AMPH-induced preference and sexual motivation. Our molecular dynamics simulations of the DAT/Stx1 complex demonstrate that phosphorylation of these proteins is pivotal for DAT to dwell in a DA releasing state. This state is characterized by the breakdown of two key salt bridges within the DAT intracellular gate, causing the opening and hydration of the DAT intracellular vestibule, allowing DA to bind from the cytosol, a mechanism that we hypothesize underlies nonvesicular DA release. |
| Volume | 9(2) |
| Pages | eadd8417 |
| Published | 2023-1-13 |
| DOI | 10.1126/sciadv.add8417 |
| PMID | 36630507 |
| PMC | PMC9833662 |
| MeSH | Amphetamine / pharmacology Animals Dopamine* / metabolism Dopamine Plasma Membrane Transport Proteins / metabolism Drosophila melanogaster / metabolism Phosphorylation Syntaxin 1* / genetics Syntaxin 1* / metabolism |
| IF | 13.117 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 36 |
| Altmetric score changes over past 6months | 0.5 |
| Resource | |
| Drosophila | DGRC#109594 |