Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.
| Autor: | Saenz J; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.; Rutgers Graduate School of Biomedical Sciences, Molecular Biosciences Graduate Program, 675 Hoes Lane West, Piscataway, NJ 08854, USA., Khezerlou E; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA., Aggarwal M; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA., Shaikh A; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA., Ganti N; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA., Herborg F; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark., Pan PY; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Research square [Res Sq] 2024 Mar 13. Date of Electronic Publication: 2024 Mar 13. |
| DOI: | 10.21203/rs.3.rs-4021466/v1 |
| Abstrakt: | Missense mutations of PARK20/ SYNJ1 (synaptojanin1/Synj1) have been linked to complex forms of familial parkinsonism, however, the molecular and cellular changes associated with dopaminergic dysfunction remains unknown. We now report fast depletion of evoked dopamine (DA) and altered maintenance of the axonal dopamine transporter (DAT) in the Synj1+/- neurons. While Synj1 has been traditionally known to facilitate the endocytosis of synaptic vesicles, we demonstrated that axons of cultured Synj1+/- neurons exhibit an increase of total DAT but a reduction of the surface DAT, which could be exacerbated by neuronal activity. We revealed that the loss of surface DAT is specifically associated with the impaired 5'-phosphatase activity of Synj1 and the hyperactive downstream PI(4,5)P Competing Interests: Conflict of Interests The authors declare no competing interests. |
| Databáze: | MEDLINE |
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