|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 15, 13219-13228, April 12, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Kv
Genetic Analysis of the Mammalian K+ Channel
Subunit Kv2 (Kcnab2)*
§¶
,**,
Department of Pathobiological Sciences and
the Waisman Center, University of Wisconsin, Madison, Wisconsin
53705-2280 and the § Laboratory of Genetics, the
¶ Department of Physiology, and the ** Neuroscience
Training Program, University of Wisconsin,
Madison, Wisconsin 53706
2 binds to K+ channel 
subunits from at least two different families (Kv1 and Kv4) and is a
member of the aldo-ketoreductase (AKR) superfamily. Proposed functions
for this protein in vivo include a chaperone-like role in
Kv1 subunit biogenesis and catalytic activity as an AKR
oxidoreductase. To investigate the in vivo function of
Kv2, Kv2-null and point mutant (Y90F) mice were generated through
gene targeting in embryonic stem cells. In Kv2-null mice, Kv1.1 and
Kv1.2 localize normally in cerebellar basket cell terminals and the
juxtaparanodal region of myelinated nerves. Moreover, normal
glycosylation patterns are observed for Kv1.1 and Kv1.2 in whole brain
lysates. Thus, loss of the chaperone-like activity does not appear to
account for the phenotype of Kv2-null mice, which include reduced
life spans, occasional seizures, and cold swim-induced tremors similar
to that observed in Kv1.1-null mice. Mice expressing Kv2, mutated at
a site (Y90F) that abolishes AKR-like catalytic activity in other
family members, have no overt phenotype. We conclude that Kv2
contributes to regulation of excitability in vivo, although
not directly through either chaperone-like or typical AKR catalytic
activity. Rather, Kv2 relies upon as yet unidentified mechanisms in
the regulation of K+ channel and/or oxidoreductive functions.
*
This work was supported by National Institutes of Health
Grants GM-18420 (to K. M.), NS-15390 (to B. G.), and NS-23375
(to S. Y. C. and A. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Aurora
Biosciences, Inc., 11010 Torreyana Rd., La Jolla, CA 92121. Tel.: 858-404-8448; Fax: 858-404-6719; E-mail:
mccormackk@aurorabio.com.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. H. Pineda, C. S. Knoeckel, A. D. Taylor, A. Estrada-Bernal, and A. B. Ribera Kv1 Potassium Channel Complexes In Vivo Require Kv{beta}2 Subunits in Dorsal Spinal Neurons J Neurophysiol, October 1, 2008; 100(4): 2125 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Brew, J. X. Gittelman, R. S. Silverstein, T. D. Hanks, V. P. Demas, L. C. Robinson, C. A. Robbins, J. McKee-Johnson, S. Y. Chiu, A. Messing, et al. Seizures and Reduced Life Span in Mice Lacking the Potassium Channel Subunit Kv1.2, but Hypoexcitability and Enlarged Kv1 Currents in Auditory Neurons J Neurophysiol, September 1, 2007; 98(3): 1501 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. P. Torres, F. J. Morera, I. Carvacho, and R. Latorre A Marriage of Convenience: beta-Subunits and Voltage-dependent K+ Channels J. Biol. Chem., August 24, 2007; 282(34): 24485 - 24489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nesti, B. Everill, and A. D. Morielli Endocytosis as a Mechanism for Tyrosine Kinase-dependent Suppression of a Voltage-gated Potassium Channel Mol. Biol. Cell, September 1, 2004; 15(9): 4073 - 4088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Birnbaum, A. W. Varga, L.-L. Yuan, A. E. Anderson, J. D. Sweatt, and L. A. Schrader Structure and Function of Kv4-Family Transient Potassium Channels Physiol Rev, July 1, 2004; 84(3): 803 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Sokolova, A. Accardi, D. Gutierrez, A. Lau, M. Rigney, and N. Grigorieff Conformational changes in the C terminus of Shaker K+ channel bound to the rat Kv{beta}2-subunit PNAS, October 28, 2003; 100(22): 12607 - 12612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Kramer, W. J. Cook, F. P. Roth, J. Zhu, H. Holman, D. M. Knipe, and D. M. Coen Latent Herpes Simplex Virus Infection of Sensory Neurons Alters Neuronal Gene Expression J. Virol., September 1, 2003; 77(17): 9533 - 9541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M Brew, J. L Hallows, and B. L Tempel Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1 J. Physiol., April 1, 2003; 548(1): 1 - 20. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |