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Science 301 (5633): 646-649

Copyright © 2003 by the American Association for the Advancement of Science

A Conserved Domain in Axonal Targeting of Kv1 (Shaker) Voltage-Gated Potassium Channels

Chen Gu, Yuh Nung Jan, Lily Yeh Jan*

Abstract: Axonal voltage-gated potassium (Kv1) channels regulate action-potential invasion and hence transmitter release. Although evolutionarily conserved, what mediates their axonal targeting is not known. We found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 or dendritic transferrin receptor, T1 promoted their axonal surface expression. Moreover, T1 mutations eliminating Kvß association compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. Thus, proper association of Kvß with the Kv1 T1 domain is essential for axonal targeting.

Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, CA 94143–0725, USA.

* To whom correspondence should be addressed. E-mail: gkw{at}

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J. H. Hyun, K. Eom, K.-H. Lee, W.-K. Ho, and S.-H. Lee (2013)
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   Abstract »    Full Text »    PDF »
Alternative Splicing Regulates Kv3.1 Polarized Targeting to Adjust Maximal Spiking Frequency.
Y. Gu, J. Barry, R. McDougel, D. Terman, and C. Gu (2012)
J. Biol. Chem. 287, 1755-1769
   Abstract »    Full Text »    PDF »
Subunit-Dependent Axonal Trafficking of Distinct {alpha} Heteromeric Potassium Channel Complexes.
P. M. Jenkins, J. C. McIntyre, L. Zhang, A. Anantharam, E. D. Vesely, K. L. Arendt, C. J. L. Carruthers, T. K. Kerppola, J. A. Iniguez-LluhI, R. W. Holz, et al. (2011)
J. Neurosci. 31, 13224-13235
   Abstract »    Full Text »    PDF »
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C. Gu and Y. Gu (2011)
J. Biol. Chem. 286, 25835-25847
   Abstract »    Full Text »    PDF »
Optogenetic photochemical control of designer K+ channels in mammalian neurons.
D. L. Fortin, T. W. Dunn, A. Fedorchak, D. Allen, R. Montpetit, M. R. Banghart, D. Trauner, J. P. Adelman, and R. H. Kramer (2011)
J Neurophysiol 106, 488-496
   Abstract »    Full Text »    PDF »
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H. Vacher, J.-W. Yang, O. Cerda, A. Autillo-Touati, B. Dargent, and J. S. Trimmer (2011)
J. Cell Biol. 192, 813-824
   Abstract »    Full Text »    PDF »
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M. Xu, Y. Gu, J. Barry, and C. Gu (2010)
J. Neurosci. 30, 15987-16001
   Abstract »    Full Text »    PDF »
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E. Hedlund, M. Karlsson, T. Osborn, W. Ludwig, and O. Isacson (2010)
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GABAB Receptor Constituents Revealed by Tandem Affinity Purification from Transgenic Mice.
T. Bartoi, K. T. G. Rigbolt, D. Du, G. Kohr, B. Blagoev, and H.-C. Kornau (2010)
J. Biol. Chem. 285, 20625-20633
   Abstract »    Full Text »    PDF »
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B. Biermann, K. Ivankova-Susankova, A. Bradaia, S. Abdel Aziz, V. Besseyrias, J. P. Kapfhammer, M. Missler, M. Gassmann, and B. Bettler (2010)
J. Neurosci. 30, 1385-1394
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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F. Tsuruta, E. M. Green, M. Rousset, and R. E. Dolmetsch (2009)
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   Abstract »    Full Text »    PDF »
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C. Bel, K. Oguievetskaia, C. Pitaval, L. Goutebroze, and C. Faivre-Sarrailh (2009)
J. Cell Sci. 122, 3403-3413
   Abstract »    Full Text »    PDF »
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D. B. Arnold (2009)
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H. Vacher, D. P. Mohapatra, and J. S. Trimmer (2008)
Physiol Rev 88, 1407-1447
   Abstract »    Full Text »    PDF »
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Y. Ogawa, I. Horresh, J. S. Trimmer, D. S. Bredt, E. Peles, and M. N. Rasband (2008)
J. Neurosci. 28, 5731-5739
   Abstract »    Full Text »    PDF »
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D. P. Mohapatra, D. F. Siino, and J. S. Trimmer (2008)
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   Abstract »    Full Text »    PDF »
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C. C. Yap, R. L. Nokes, D. Wisco, E. Anderson, H. Folsch, and B. Winckler (2008)
J. Cell Sci. 121, 1514-1525
   Abstract »    Full Text »    PDF »
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Y. Pan, J. Weng, Y. Cao, R. C. Bhosle, and M. Zhou (2008)
J. Biol. Chem. 283, 8634-8642
   Abstract »    Full Text »    PDF »
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M. Xu, R. Cao, R. Xiao, M. X. Zhu, and C. Gu (2007)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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