DPP6 Domains Responsible for Its Localization and Function

Abstract

Background: DPP6, a transmembrane protein with a large extracellular domain, is an auxiliary subunit of Kv4.2 potassium channels. Results: The extracellular domain is required for DPP6 export from the ER while intracellular domains impart the functional impact on Kv4.2. Conclusion: Different DPP6 domains are responsible for its localization and function. Significance: Understanding DPP6 function may provide insight into its role in neuronal development and disease.

Kv4.2 and Accessory Dipeptidyl Peptidase-like Protein 10 (DPP10) Subunit Preferentially Form a 4:2 (Kv4.2:DPP10) Channel Complex

“…First, we injected cRNA of mEGFP-DPP10-D-Extra (2 ng) alone and observed the expression in Xenopus oocytes. This was well expressed on the cell surface, in agreement with Lin et al (41). Most of the fluorescent spots were mobile (supplemental Movie 3), in sharp contrast to mEGFP-DPP10 with the extracellular domain, which mostly stayed in the same place (supplemental Movie 1).…”

“…The two fragments were ligated at the XhoI sites and inserted into the KpnI and BstXI sites in the DPP10-pGEMHE construct. A C-terminal truncated version of mEGFP-DPP10 (mEGFP-DPP10-D-Extra) was made by PCR as described previously (41). To construct Kv4.2-mCherry, a BglII site was introduced into the N terminus of mCherry with a flexible GGS linker (BglII-mCherry).…”

“…Because the extracellular domain is large (residues 50 -789) and bulky, we predicted that a deletion of the extracellular domain might change the preference of the 4:2 stoichiometry in the Kv4.2-DPP10 complex. Lin et al (41) recently made the deletion mutant of DPP6 (DPP6-D-Extra), which lacks the entire C-terminal extracellular domain. Interestingly, DPP6-D-Extra is very well expressed on the cell surface of HEK293 cells and accelerates the recovery from inactivation, yet it fails to increase the current amplitude (41).…”

“…Lin et al (41) recently made the deletion mutant of DPP6 (DPP6-D-Extra), which lacks the entire C-terminal extracellular domain. Interestingly, DPP6-D-Extra is very well expressed on the cell surface of HEK293 cells and accelerates the recovery from inactivation, yet it fails to increase the current amplitude (41). To examine whether the extracellular domain has an influence on the stoichiometry of Kv4.2-DPP10, we made a similar C-terminal deletion mutant, DPP10-D-Extra, which lacks the entire extracellular domain (residues 50 -789) (Fig.…”

Genetics of Common Antipsychotic-Induced Adverse Effects

“…DPP6 encodes dipeptidyl peptidase protein 6, an auxiliary subunit of kv4.2 voltage-gated potassium channels [148]. Using the same discovery sample and a similar methodological approach to that of the Japanese study on HSPG2 (though this time utilizing a different SNP array), the same research team detected an association between the DPP6 intronic SNP rs6977820 and TD [149].…”