|
|
|
|
|
|
|
||
ARTICLE |
Correspondence to Manuel Covarrubias: Manuel.Covarrubias{at}jefferson.edu
Dipeptidyl aminopeptidase–like proteins (DPLPs) interact with Kv4 channels and thereby induce a profound remodeling of activation and inactivation gating. DPLPs are constitutive components of the neuronal Kv4 channel complex, and recent observations have suggested the critical functional role of the single transmembrane segment of these proteins (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. J. Biol. Chem. 280:18853–18861). However, the underlying mechanism of action is unknown. We hypothesized that a unique interaction between the Kv4.2 channel and a DPLP found in brain (DPPX-S) may remodel the channel's voltage-sensing domain. To test this hypothesis, we implemented a robust experimental system to measure Kv4.2 gating currents and study gating charge dynamics in the absence and presence of DPPX-S. The results demonstrated that coexpression of Kv4.2 and DPPX-S causes a –26 mV parallel shift in the gating charge-voltage (Q-V) relationship. This shift is associated with faster outward movements of the gating charge over a broad range of relevant membrane potentials and accelerated gating charge return upon repolarization. In sharp contrast, DPPX-S had no effect on gating charge movements of the Shaker B Kv channel. We propose that DPPX-S destabilizes resting and intermediate states in the voltage-dependent activation pathway, which promotes the outward gating charge movement. The remodeling of gating charge dynamics may involve specific protein–protein interactions of the DPPX-S's transmembrane segment with the voltage-sensing and pore domains of the Kv4.2 channel. This mechanism may determine the characteristic fast operation of neuronal Kv4 channels in the subthreshold range of membrane potentials.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. H. Jerng and P. J. Pfaffinger Multiple Kv Channel-interacting Proteins Contain an N-terminal Transmembrane Domain That Regulates Kv4 Channel Trafficking and Gating J. Biol. Chem., December 19, 2008; 283(51): 36046 - 36059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Maffie and B. Rudy Weighing the evidence for a ternary protein complex mediating A-type K+ currents in neurons J. Physiol., December 1, 2008; 586(23): 5609 - 5623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kim, M. S. Nadal, A. M. Clemens, M. Baron, S.-C. Jung, Y. Misumi, B. Rudy, and D. A. Hoffman Kv4 Accessory Protein DPPX (DPP6) is a Critical Regulator of Membrane Excitability in Hippocampal CA1 Pyramidal Neurons J Neurophysiol, October 1, 2008; 100(4): 1835 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Soh and S. A. N. Goldstein ISA Channel Complexes Include Four Subunits Each of DPP6 and Kv4.2 J. Biol. Chem., May 30, 2008; 283(22): 15072 - 15077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Amarillo, J. A. De Santiago-Castillo, K. Dougherty, J. Maffie, E. Kwon, M. Covarrubias, and B. Rudy Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons J. Physiol., April 15, 2008; 586(8): 2093 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dougherty, J. A. De Santiago-Castillo, and M. Covarrubias Gating Charge Immobilization in Kv4.2 Channels: The Basis of Closed-State Inactivation J. Gen. Physiol., February 25, 2008; 131(3): 257 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Barghaan, M. Tozakidou, H. Ehmke, and R. Bahring Role of N-Terminal Domain and Accessory Subunits in Controlling Deactivation-Inactivation Coupling of Kv4.2 Channels Biophys. J., February 15, 2008; 94(4): 1276 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
