DOI: 10.1126/science.1086998. A Conserved Domain in Axonal Targeting of Kv1 (Shaker) Voltage-Gated Potassium Channels

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

10.1126/science.1086998

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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 Kvβ association compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. Thus, proper association of Kvβ with the Kv1 T1 domain is essential for axonal targeting.

Bibliography

Gu, C., Jan, Y. N., & Jan, L. Y. (2003). A Conserved Domain in Axonal Targeting of Kv1 (Shaker) Voltage-Gated Potassium Channels. Science, 301(5633), 646â649.

Authors 3

Chen Gu (first)
Yuh Nung Jan (additional)
Lily Yeh Jan (additional)

References 25 Referenced 137

10.1113/jphysiol.1952.sp004717
D. Debanne, N. C. Guerineau, B. H. Gahwiler, S. M. Thompson, Nature390, 536 (1997). / Nature (1997)
S. A. Baccus, B. D. Burrell, C. L. Sahley, K. J. Muller, J. Neurophysiol.83, 1693 (2000). (10.1152/jn.2000.83.3.1693) / J. Neurophysiol. (2000)
D. L. Brody, D. T. Yue, J. Neurosci.20, 2480 (2000). (10.1523/JNEUROSCI.20-07-02480.2000) / J. Neurosci. (2000)
E. K. Lambe, G. K. Aghajanian, J. Neurosci.21, 9955 (2001). (10.1523/JNEUROSCI.21-24-09955.2001) / J. Neurosci. (2001)
M. M. Monaghan, J. S. Trimmer, K. J. Rhodes, J. Neurosci.21, 5973 (2001). (10.1523/JNEUROSCI.21-16-05973.2001) / J. Neurosci. (2001)
10.1016/S0896-6273(00)81018-1
L. Zhou, C. L. Zhang, A. Messing, S. Y. Chiu, J. Neurosci.18, 7200 (1998). (10.1523/JNEUROSCI.18-18-07200.1998) / J. Neurosci. (1998)
D. L. Browne et al., Nature Genet.8, 136 (1994). (10.1038/ng1094-136) / Nature Genet. (1994)
10.1126/science.2441470
C. R. Campomaneset al., J. Biol. Chem.277, 8298 (2002). (10.1074/jbc.M110276200) / J. Biol. Chem. (2002)
10.1074/jbc.M005010200
J. F. Rivera, S. Ahmad, M. W. Quick, E. R. Liman, D. B. Arnold, Nature Neurosci.6, 243 (2003). (10.1038/nn1020) / Nature Neurosci. (2003)
10.1016/S0896-6273(03)00058-8
Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; X any amino acid; Y Tyr; and Φ hydrophobic amino acids.
10.1126/science.291.5502.316
D. Hattan, E. Nesti, T. G. Cachero, A. D. Morielli, J. Biol. Chem.277, 38596 (2002). (10.1074/jbc.M205005200) / J. Biol. Chem. (2002)
10.1126/science.1519059
A. Kosolapov, C. Deutsch, J. Biol. Chem.278, 4305 (2003). (10.1074/jbc.M209422200) / J. Biol. Chem. (2003)
C. T. Schulteis, N. Nagaya, D. M. Papazian, J. Biol. Chem.273, 26210 (1998). (10.1074/jbc.273.40.26210) / J. Biol. Chem. (1998)
D. L. Minor et al., Cell102, 657 (2000). (10.1016/S0092-8674(00)00088-X) / Cell (2000)
M. A. Burack, M. A. Silverman, G. Banker, Neuron26, 465 (2000). (10.1016/S0896-6273(00)81178-2) / Neuron (2000)
10.1126/science.289.5476.123
O. Fili et al., J. Neurosci.21, 1964 (2001). (10.1523/JNEUROSCI.21-06-01964.2001) / J. Neurosci. (2001)
We thank J. Trimmer and Y. Hong for antibodies G. Banker for the TfR-GFP construct and members of the Jan lab for comments on the manuscript. This study is supported by an NIMH center grant to L.Y.J. Y.N.J. and L.Y.J. are Howard Hughes Medical Institute investigators.

Dates

Type	When
Created	22 years, 1 month ago (July 31, 2003, 11:27 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:40 p.m.)
Indexed	3 weeks, 6 days ago (Aug. 7, 2025, 4:26 p.m.)
Issued	22 years, 1 month ago (Aug. 1, 2003)
Published	22 years, 1 month ago (Aug. 1, 2003)
Published Print	22 years, 1 month ago (Aug. 1, 2003)

Funders 0

None

BibTeX

@article{Gu_2003, title={A Conserved Domain in Axonal Targeting of Kv1 (Shaker) Voltage-Gated Potassium Channels}, volume={301}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1086998}, DOI={10.1126/science.1086998}, number={5633}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Gu, Chen and Jan, Yuh Nung and Jan, Lily Yeh}, year={2003}, month=aug, pages={646–649} }

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