RGD Reference Report - Regulation of dopamine transporter activity by carboxypeptidase E. - Rat Genome Database

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Regulation of dopamine transporter activity by carboxypeptidase E.

Authors: Zhang, H  Li, S  Wang, M  Vukusic, B  Pristupa, ZB  Liu, F 
Citation: Zhang H, etal., Mol Brain. 2009 May 6;2:10.
RGD ID: 6483104
Pubmed: PMID:19419578   (View Abstract at PubMed)
PMCID: PMC2687442   (View Article at PubMed Central)
DOI: DOI:10.1186/1756-6606-2-10   (Journal Full-text)

BACKGROUND: The dopamine transporter (DAT) plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT) can directly interact with other cellular proteins and regulate DAT function and trafficking. RESULTS: 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. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. 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. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. CONCLUSION: 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.




Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Slc6a3Ratprotease binding  IPICpe (Rattus norvegicus) RGD 
CpeRatprotein binding  IPISlc6a3 (Rattus norvegicus) RGD 


Genes (Rattus norvegicus)
Cpe  (carboxypeptidase E) Slc6a3  (solute carrier family 6 member 3)