Specifically, immunoelectron microscopy studies find that DAT is located peri-synaptically, indicating that transmitter released at the synapse diffuses out of the cleft to be transported into the terminal. Morphological studies reveal that functional DATs are localized on the plasma membrane of axons, pre-synaptic axon terminals, and dendrites of dopaminergic neurons, with the highest expression in the axonal processes in striatum and dendrites in ventral tegmental area. Moreover, the DAT has garnered attention because it is the principle target of widely abused psychostimulants, such as cocaine and amphetamine. Dopamine (DA), an essential neurotransmitter for normal CNS functions including motor activity, cognition and reward, which is involved in numerous neurological disorders including Parkinson's disease, drug addiction and schizophrenia, is primarily cleared from the synapse. DAT belongs to a family of Na+/Cl- dependent transporters with several other neurotransmitter transporters, including norepinephrine, serotonin, GABA, and glycine transporters. The dopamine transporter (DAT) is a presynaptic plasma protein found on dopaminergic nerve terminals that terminates dopamine signaling by rapidly sequestering dopamine released into the synaptic cleft. Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity. ![]() In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Here, we have identified that carboxypeptidase E (CPE), a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT) can directly interact with other cellular proteins and regulate DAT function and trafficking. The dopamine transporter (DAT) plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |