DPP6 Membrane Protein Introduction

Introduction of DPP6

DPP6 is a type II transmembrane protein that consists of a single transmembrane domain and a short intracellular N-terminus. DPP6 belongs to the prolyl oligopeptidase family of serine proteases. DPP6 is encoded by the DPP6 gene which is located at 7q36.2, and mutations of the gene can cause familial paroxysmal ventricular fibrillation 2 as well as mental retardation, autosomal dominant 33 (MRD33). The molecular mass is about 97 KDa.

Function of DPP6 Membrane Protein

DPP6 is an auxiliary subunit of the Kv4 family of voltage-gated K⁺ channels. It has been shown that DPP6 can enhance potassium channel surface expression and potently accelerate their kinetics. It is expressed predominantly in brain and exists as several splicing variants termed DPPX-L, DPPX-S, DPPX-N, and DPPX-O. DPP6 also participates in many biological processes, such as protein localization to plasma membrane and regulation of potassium ion transmembrane transport. On the other hand, DPP6 is also known for its large extracellular domain which is required for its export from the ER and expression and stabilization on the cell surface. At the same time, the short intracellular N-terminal of DPP6 and its transmembrane domains associates with and accelerates the recovery from inactivation of Kv4.2. In detail, a cysteine-rich motif included in extracellular domain plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER.

Fig.1 Structure of DPP6 membrane protein (Strop, 2004).

Application of DPP6 Membrane Protein in Literature

1. Lainez S., et al. Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual K⁺ channel activator NS3623. Biochemical Pharmacology. 2018, 150:120-130. PubMed ID: 29378180
   
   

   This article reports that KChIP2 isoforms and DPP6 proteins are not required for Kv4.3 activation by NS3623, but their presence influences the compound’s effects on the rate of current decay, dominating the overall effect as reflected by total charge transfer (AUC).

2. Lin L., et al. DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory. Frontiers in Cellular Neuroscience. 2018, 12:84. PubMed ID: 29651237
   
   

   This article focuses on the behavioral consequences of DPP6 loss, the authors find that DPP6 knockout (DPP6-KO) mice are impaired in hippocampus-dependent learning and memory. Moreover, impaired synaptic development along with spatial learning and memory deficiencies in DPP6-KO mice.

3. Ten Sande J.N., et al. Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus. Heart Rhythm. 2016, 13(4):905-912. PubMed ID: 26681609
   
   

   Authors in this group studied 601 family members and probands: 286 DPP6 risk-haplotype positive (haplotype-positive) and 315 DPP6 risk-haplotype negative (haplotype-negative) individuals. However, they find there were no differences in electrocardiographic indices between haplotype-positives and haplotype-negatives, or between haplotype-positives with or without events.

4. Balhuizen A., et al. A sdAb-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells. Sci Rep. 2017, 7(1):15130. PubMed ID: 29123178
   
   

   Authors in this article identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells.

5. Lin L., et al. DPP6 domains responsible for its localization and function. Journal of Biological Chemistry. 2014, 289(46):32153-65. PubMed ID: 29123178
   
   

   This article reveals that the extracellular domain and intracellular domain responsible for different biological function. In details, the extracellular domain is required for DPP6 export from the ER while intracellular domains impart the functional impact on Kv4.2.

DPP6 Preparation Options

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Reference

1. Strop P., et al. (2004). Structure of a human a-type potassium channel interacting protein DPPX, a member of the dipeptidyl aminopeptidase family. Journal of Molecular Biology, 343(4), 1055-1065.

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