PMID:15671030

Citation	Zagha, E, Ozaita, A, Chang, SY, Nadal, MS, Lin, U, Saganich, MJ, McCormack, T, Akinsanya, KO, Qi, SY and Rudy, B (2005) DPP10 modulates Kv4-mediated A-type potassium channels. J. Biol. Chem. 280:18853-61
Abstract	A new member of a family of proteins characterized by structural similarity to dipeptidyl peptidase (DPP) IV known as DPP10 was recently identified and linked to asthma susceptibility; however, the cellular functions of DPP10 are thus far unknown. DPP10 is highly homologous to subfamily member DPPX, which we previously reported as a modulator of Kv4-mediated A-type potassium channels (Nadal, M. S., Ozaita, A., Amarillo, Y., Vega-Saenz de Miera, E., Ma, Y., Mo, W., Goldberg, E. M., Misumi, Y., Ikehara, Y., Neubert, T. A., and Rudy, B. (2003) Neuron. 37, 449-461). We studied the ability of DPP10 protein to modulate the properties of Kv4.2 channels in heterologous expression systems. We found DPP10 activity to be nearly identical to DPPX activity and significantly different from DPPIV activity. DPPX and DPP10 facilitated Kv4.2 protein trafficking to the cell membrane, increased A-type current magnitude, and modified the voltage dependence and kinetic properties of the current such that they resembled the properties of A-type currents recorded in neurons in the central nervous system. Using in situ hybridization, we found DPP10 to be prominently expressed in brain neuronal populations that also express Kv4 subunits. Furthermore, DPP10 was detected in immunoprecipitated Kv4.2 channel complexes from rat brain membranes, confirming the association of DPP10 proteins with native Kv4.2 channels. These experiments suggest that DPP10 contributes to the molecular composition of A-type currents in the central nervous system. To dissect the structural determinants of these integral accessory proteins, we constructed chimeras of DPPX, DPP10, and DPPIV lacking the extracellular domain. Chimeras of DPPX and DPP10, but not DPPIV, were able to modulate the properties of Kv4.2 channels, highlighting the importance of the intracellular and transmembrane domains in this activity.
Links	PubMed Online version:10.1074/jbc.M410613200
Keywords	Amino Acid Sequence; Animals; Biotinylation; Blotting, Northern; Brain/metabolism; CHO Cells; Cell Membrane/metabolism; Central Nervous System/metabolism; Cricetinae; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/physiology; Electrophysiology; Humans; Immunoblotting; Immunohistochemistry; Immunoprecipitation; In Situ Hybridization; Kinetics; Mass Spectrometry; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Sequence Data; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/physiology; Neurons/metabolism; Peptides/chemistry; Potassium Channels/metabolism; Potassium Channels/physiology; Potassium Channels, Voltage-Gated/metabolism; Protein Conformation; Protein Structure, Tertiary; RNA/chemistry; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins/chemistry; Sequence Homology, Amino Acid; Shal Potassium Channels; Time Factors; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DPP10	involved_in	GO:1903078: positive regulation of protein localization to plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:DPP10		GO:0090004: positive regulation of establishment of protein localization in plasma membrane	ECO:0000314:		P		Figure 1d showed that DPP10 facilitated cell membrane surface expression of Kv4.2 protein through in situ hybridization. accession #:AY172661	complete CACAO 3609
RAT:DPP6		GO:0090004: positive regulation of establishment of protein localization in plasma membrane	ECO:0000314:		P		figure 1c shows that DPPX (DPP6) promoted a robust trafficking of Kv4.2 to the plasma membrane. accession #:M76427	complete CACAO 3610
RAT:DPP6	involved_in	GO:1903078: positive regulation of protein localization to plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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