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8.A.51 The Dipeptidyl-aminopeptidase-like Protein 6 beta subunit of Kv4 channels (DPP6) Family

Auxiliary beta-subunits dictate the physiological properties of voltage-gated K+ (KV) channels in excitable tissues. The dipeptidyl-aminopeptidase-like protein 6 (DPP6) is a specific β-subunit of neuronal KV4 channels, which may promote gating through interactions between the single transmembrane segment of DPP6 and the channel's voltage sensing domain (VSD) (Maffie and Rudy 2008). A combination of gating current measurements and protein biochemistry (in-vitro translation and co- immunoprecipitations) revealed preferential physical interaction between the isolated KV4.2-VSD and DPP6 (Dougherty et al. 2009). Significantly weaker interactions were detected between DPP6 and KV1.3 channels or the KV4.2 pore domain (McNicholas et al. 2009). More efficient gating charge movement resulting from a direct interaction between DPP6 and the KV4.2-VSD is unique among the known actions of KV channel beta-subunits. Thus. the modular VSD of a KV channel can be directly regulated by transmembrane protein-protein interactions involving an extrinsic β-subunit. Understanding these interactions may shed light on the pathophysiology of recently identified human disorders associated with mutations affecting the dpp6 gene. Loss of DPP6 influences neuronal excitability and promotes neurodegnerative dementia (Cacace et al. 2019).

 

This family belongs to the: Hydrolase Superfamily.

References associated with 8.A.51 family:

Cacace, R., B. Heeman, S. Van Mossevelde, A. De Roeck, J. Hoogmartens, P. De Rijk, H. Gossye, K. De Vos, W. De Coster, M. Strazisar, G. De Baets, J. Schymkowitz, F. Rousseau, N. Geerts, T. De Pooter, K. Peeters, A. Sieben, J.J. Martin, S. Engelborghs, E. Salmon, P. Santens, R. Vandenberghe, P. Cras, P. P De Deyn, J. C van Swieten, C. M van Duijn, J. van der Zee, K. Sleegers, C. Van Broeckhoven, and. (2019). Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability. Acta Neuropathol. [Epub: Ahead of Print] 30874922
Dougherty, K. and M. Covarrubias. (2006). A dipeptidyl aminopeptidase-like protein remodels gating charge dynamics in Kv4.2 channels. J Gen Physiol 128: 745-753. 17130523
Dougherty, K., L. Tu, C. Deutsch, and M. Covarrubias. (2009). The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting β-subunit of neuronal K(V)4.2 channels. Channels (Austin) 3: 122-128. 19372736

References associated with 8.a.51 family:

Fang, J. and Y. Wei. (2011). Expression, purification and characterization of the Escherichia coli integral membrane protein YajC. Protein Pept Lett 18: 601-608. 21235483
Gardel, C., K. Johnson, A. Jacq and J. Beckwith (1990). The secD locus of E. coli codes for two membrane proteins required for protein export. EMBO J. 9: 3209-3216. 2170107

References associated with 8.A.51 family:

Kuo, Y.L., J.K. Cheng, W.H. Hou, Y.C. Chang, P.H. Du, J.J. Jian, R.H. Rau, J.H. Yang, C.C. Lien, and M.L. Tsaur. (2017). K+ Channel Modulatory Subunits KChIP and DPP Participate in Kv4-Mediated Mechanical Pain Control. J. Neurosci. 37: 4391-4404. 28330877
Maffie, J. and B. Rudy. (2008). Weighing the evidence for a ternary protein complex mediating A-type K+ currents in neurons. J. Physiol. 586: 5609-5623. 18845608
McNicholas, K., T. Chen, and C.A. Abbott. (2009). Dipeptidyl peptidase (DP) 6 and DP10: novel brain proteins implicated in human health and disease. Clin Chem Lab Med 47: 262-267. 19676137
Ren, X., Y. Hayashi, N. Yoshimura, and K. Takimoto. (2005). Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels. Mol. Cell Neurosci 29: 320-332. 15911355

References associated with 8.a.51 family:

Reuter, K., R. Slany, F. Ullrich and H. Kersten (1991). Structure and organization of Escherichia coli genes involved in biosynthesis of the deazaguanine derivative queuine, a nutrient factor for eukaryotes. J. Bacteriol. 173: 2256-2264. 1706703
Törnroth-Horsefield, S., P. Gourdon, R. Horsefield, L. Brive, N. Yamamoto, H. Mori, A. Snijder, and R. Neutze. (2007). Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist. Structure. 15: 1663-1673. 18073115

References associated with 8.A.51 family:

Zagha, E., A. Ozaita, S.Y. Chang, M.S. Nadal, U. Lin, M.J. Saganich, T. McCormack, K.O. Akinsanya, S.Y. Qi, and B. Rudy. (2005). DPP10 modulates Kv4-mediated A-type potassium channels. J. Biol. Chem. 280: 18853-18861. 15671030