Dopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson's disease

Neurobiology of Disease

卷:36

Diego Álvarez de la Rosa¹  Tomas González-Hernández²  Manuel Rodríguez³  Domingo Afonso-Oramas⁴  Josmar Salas-Hernández⁴  José L. Lanciego⁴  Ignacio Cruz-Muros⁴  Pedro Abreu⁵  Teresa Giráldez⁶  Javier Castro-Hernández⁷ 

[1] Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain;

[2] Centro de Investigación Médica Aplicada, Universidad de Navarra, Spain;

[3] Departamento de Anatomía, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain;

[4] Departamento de Farmacología, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain;

[5] Departamento de Fisiología, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain;

[6] Unidad de Investigación, Hospital Universitario Ntra Sra de Candelaria, Tenerife, Spain;

关键词: Parkinson's disease;    Pathogenesis;    Dopamine transporter;    Glycosylation;    Differential vulnerability;   

DOI  :  

来源: DOAJ

【 摘 要 】

The dopamine transporter (DAT) is a membrane glycoprotein responsible for dopamine (DA) uptake, which has been involved in the degeneration of DA cells in Parkinson's disease (PD). Given that DAT activity depends on its glycosylation status and membrane expression, and that not all midbrain DA cells show the same susceptibility to degeneration in PD, we have investigated a possible relationship between DAT glycosylation and function and the differential vulnerability of DA cells. Glycosylated DAT expression, DA uptake, and DAT Vmax were significantly higher in terminals of nigrostriatal neurons than in those of mesolimbic neurons. No differences were found in non-glycosylated DAT expression and DAT Km, and DA uptake differences disappeared after deglycosylation of nigrostriatal synaptosomes. The expression pattern of glycosylated DAT in the human midbrain and striatum showed a close anatomical relationship with DA degeneration in parkinsonian patients. This relationship was confirmed in rodent and monkey models of PD, and in HEK cells expressing the wild-type and a partially deglycosylated DAT form. These results strongly suggest that DAT glycosylation is involved in the differential vulnerability of midbrain DA cells in PD.

【 授权许可】

Unknown