Title : N-glycosylation of the mammalian
dipeptidyl aminopeptidase-like protein 10 (
DPP10 ) regulates trafficking and interaction with
Kv4 channels
Abstract :
- The dipeptidyl aminopeptidase-like protein 10 ( DPP10 ) is a type II transmembrane protein homologue to the serine protease DPPIV / CD26 but enzymatically inactive
- In the mammalian brain, DPP10 forms a complex with voltage-gated potassium channels of the Kv4 family, regulating their cell surface expression and biophysical properties
- DPP10 is a glycoprotein containing eight predicted N-glycosylation sites in the extracellular domain
- In this study we investigated the role of N-glycosylation on DPP10 trafficking and functional activity
- Using site-directed mutagenesis (N to Q) we showed that N-glycosylation occured at six positions
- Glycosylation at these specific residues was necessary for DPP10 trafficking to the plasma membrane as observed by flow cytometry
- The surface expression levels of the substitutions N90Q, N119Q, N257Q and N342Q were reduced by more than 60%
- Hence the interaction with the Kv4.3 / KChIP2a channel complex was disrupted preventing the hastening effect of wild type DPP10 on current kinetics
- Interestingly, N257 was crucial for this function and its substitution to glutamine completely blocked DPP10 sorting to the cell surface and prevented DPP10 dimerization
- In summary, we demonstrated that glycosylation was necessary for both DPP10 trafficking to the cell surface and functional interaction with Kv4 channels