Clonorchis sinensis dopamine transporter (CsDAT) facilitates dopamine uptake
Wang-Jong Lee1,2, Sung-Jun Kim3, Woon Kyu Lee4
1Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
Parasites, Hosts and Diseases
|September 1, 2025
Summary
This study characterized the Clonorchis sinensis dopamine transporter (CsDAT), finding it efficiently transports dopamine. Its unique structure and inhibitor binding offer potential for new clonorchiasis treatments.
Area of Science:
- Parasitology
- Neuroscience
- Biochemistry
Background:
- Clonorchis sinensis causes clonorchiasis, a liver fluke infection linked to hepatobiliary diseases in East Asia.
- Dopamine, a neurotransmitter, may play a role in parasite physiology and survival through uptake by trematodes.
Purpose of the Study:
- To functionally and structurally characterize the dopamine transporter (CsDAT) in C. sinensis.
- To investigate the potential of CsDAT as a therapeutic target for clonorchiasis.
Main Methods:
- Synthesized cDNA from adult C. sinensis worms and expressed CsDAT in Xenopus laevis oocytes.
- Conducted radiolabeled dopamine uptake assays and analyzed kinetic parameters.
- Constructed a 3D model of CsDAT and performed molecular docking simulations.
Main Results:
- CsDAT mediates sodium-dependent, saturable dopamine uptake with high affinity (Km = 454.5 nM).
- The 3D model revealed a conserved substrate-binding pocket with key residues interacting with dopamine.
- CsDAT exhibited higher binding affinity for dopamine and inhibitors compared to the human dopamine transporter.
Conclusions:
- CsDAT is a physiologically relevant dopamine transporter in C. sinensis.
- The distinct structural and binding properties of CsDAT suggest its potential as a specific therapeutic target for clonorchiasis, minimizing host side effects.
Keywords:
Clonorchis sinensisXenopus laevis oocytedopaminedopamine transportersolute carrier family 6 member 3uptakeMore Related Videos
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