The Surprising Catch of a Voltage-Gated Potassium Channel in a Neuronal SNARE
Abstract
Among ion channels, voltage-gated calcium channels have been considered unique in their ability to mediate signaling events independent of the flow of ions through their pore. A voltage-gated potassium channel termed Kv2.1 has been identified as playing a role remarkably similar to one ion-independent function of calcium channels, facilitating regulated exocytosis through a direct interaction with a t-SNARE [soluble NSF (N-ethylmaleimide–sensitive factor) attachment protein receptor] component of the vesicle release machinery. Kv2.1 overexpression enhances depolarization-induced secretion from the neuroendocrine-like PC12 cell line, and a nonconducting Kv2.1 mutant can accomplish the same feat. Kv2.1 interacts directly with syntaxin 1A, a plasma membrane t-SNARE component of the vesicle docking and fusion apparatus. Deletion of the syntaxin 1A–binding segment from Kv2.1 abolishes its ability to promote vesicle release, supporting a mechanism whereby Kv2.1 presumably transfers voltage-dependent conformational changes induced by membrane depolarization to interacting t-SNAREs to affect exocytosis. Kv2.1, a major mediator of electrical events in central neurons, cardiac and smooth muscle, and pancreatic β cells, must now also be recognized as a physical mediator of secretion. That Kv2.1 is phosphorylated at numerous sites within the syntaxin 1A binding segment raises the possibility that its role in secretion may be dynamically regulated by diverse signaling events.
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References
1.
B. Hille, Ionic Channels of Excitable Membranes (Sinauer, Sunderland, MA, ed. 3, 2001).
2.
W. A. Catterall, Interactions of presynaptic Ca2+ channels and snare proteins in neurotransmitter release. Ann. N. Y. Acad. Sci. 868, 144–159 (1999).
3.
P. D. Dodson, I. D. Forsythe, K. Presynaptic, + channels: Electrifying regulators of synaptic terminal excitability. Trends Neurosci. 27, 210–217 (2004).
4.
D. Singer-Lahat, A. Sheinin, D. Chikvashvili, S. Tsuk, D. Greitzer, R. Friedrich, L. Feinshreiber, U. Ashery, M. Benveniste, E. S. Levitan, I. Lotan, K+ channel facilitation of exocytosis by dynamic interaction with syntaxin. J. Neurosci. 27, 1651–1658 (2007).
5.
M. K. Bennett, N. Calakos, R. H. Scheller, Syntaxin: A synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257, 255–259 (1992).
6.
J. S. Trimmer, K. J. Rhodes, Localization of voltage-gated ion channels in mammalian brain. Annu. Rev. Physiol. 66, 477–519 (2004).
7.
S. A. Malin, J. M. Nerbonne, Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons. J. Neurosci. 22, 10094–10105 (2002).
8.
H. Murakoshi, J. S. Trimmer, Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons. J. Neurosci. 19, 1728–1735 (1999).
9.
S. Pal, K. A. Hartnett, J. M. Nerbonne, E. S. Levitan, E. Aizenman, Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels. J. Neurosci. 23, 4798–4802 (2003).
10.
J. Du, L. L. Haak, E. Phillips-Tansey, J. T. Russell, C. J. McBain, Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1. J. Physiol. 522, 19–31 (2000).
11.
D. M. Barry, J. M. Nerbonne, Myocardial potassium channels: Electrophysiological and molecular diversity. Annu. Rev. Physiol. 58, 363–394 (1996).
12.
R. H. Cox, Molecular determinants of voltage-gated potassium currents in vascular smooth muscle. Cell Biochem. Biophys. 42, 167–195 (2005).
13.
P. E. MacDonald, X. F. Ha, J. Wang, S. R. Smukler, A. M. Sun, H. Y. Gaisano, A. M. Salapatek, P. H. Backx, M. B. Wheeler, Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol. Endocrinol. 15, 1423–1435 (2001).
14.
P. E. MacDonald, G. Wang, S. Tsuk, C. Dodo, Y. Kang, L. Tang, M. B. Wheeler, M. S. Cattral, J. R. Lakey, A. M. Salapatek, I. Lotan, H. Y. Gaisano, Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus. Mol. Endocrinol. 16, 2452–2461 (2002).
15.
Y. M. Leung, Y. Kang, X. Gao, F. Xia, H. Xie, L. Sheu, S. Tsuk, I. Lotan, R. G. Tsushima, H. Y. Gaisano, Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking. J. Biol. Chem. 278, 17532–17538 (2003).
16.
T. Wolf-Goldberg, I. Michaelevski, L. Sheu, H. Y. Gaisano, D. Chikvashvili, I. Lotan, Target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (t-SNAREs) differently regulate activation and inactivation gating of Kv2.2 and Kv2.1: Implications on pancreatic islet cell Kv channels. Mol. Pharmacol. 70, 818–828 (2006).
17.
P. I. Hanson, J. E. Heuser, R. Jahn, Neurotransmitter release - four years of SNARE complexes. Curr. Opin. Neurobiol. 7, 310–315 (1997).
18.
L. A. Greene, A. S. Tischler, Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc. Natl. Acad. Sci. U.S.A. 73, 2424–2428 (1976).
19.
N. Sharma, G. D'Arcangelo, A. Kleinlaus, S. Halegoua, J. S. Trimmer, Nerve growth factor regulates the abundance and distribution of K+ channels in PC12 cells. J. Cell Biol. 123, 1835–1843 (1993).
20.
I. Michaelevski, D. Chikvashvili, S. Tsuk, D. Singer-Lahat, Y. Kang, M. Linial, H. Y. Gaisano, O. Fili, I. Lotan, Direct interaction of target SNAREs with the Kv2.1 channel. Modal regulation of channel activation and inactivation gating. J. Biol. Chem. 278, 34320–34330 (2003).
21.
F. Xia, X. Gao, E. Kwan, P. P. Lam, L. Chan, K. Sy, L. Sheu, M. B. Wheeler, H. Y. Gaisano, R. G. Tsushima, Disruption of pancreatic beta-cell lipid rafts modifies Kv2.1 channel gating and insulin exocytosis. J. Biol. Chem. 279, 24685–24691 (2004).
22.
M. B. Jackson, E. R. Chapman, Fusion pores and fusion machines in Ca2+-triggered exocytosis. Annu. Rev. Biophys. Biomol. Struct. 35, 135–160 (2006).
23.
B. A. Scalettar, How neurosecretory vesicles release their cargo. Neuroscientist 12, 164–176 (2006).
24.
Y. M. Leung, Y. Kang, F. Xia, L. Sheu, X. Gao, H. Xie, R. G. Tsushima, H. Y. Gaisano, Open form of syntaxin-1A is a more potent inhibitor than wild-type syntaxin-1A of Kv2.1 channels. Biochem. J. 387, 195–202 (2005).
25.
S. Tsuk, I. Michaelevski, G. N. Bentley, R. H. Joho, D. Chikvashvili, I. Lotan, Kv2.1 channel activation and inactivation is influenced by physical interactions of both syntaxin 1A and the syntaxin 1A/soluble N-ethylmaleimide-sensitive factor-25 (t-SNARE) complex with the C terminus of the channel. Mol. Pharmacol. 67, 480–488 (2005).
26.
M. Ludwig, Q. J. Pittman, Talking back: Dendritic neurotransmitter release. Trends Neurosci. 26, 255–261 (2003).
27.
M. Kataoka, R. Kuwahara, S. Iwasaki, Y. Shoji-Kasai, M. Takahashi, Nerve growth factor-induced phosphorylation of SNAP-25 in PC12 cells: A possible involvement in the regulation of SNAP-25 localization. J. Neurochem. 74, 2058–2066 (2000).
28.
L. H. Chamberlain, R. D. Burgoyne, G. W. Gould, SNARE proteins are highly enriched in lipid rafts in PC12 cells: Implications for the spatial control of exocytosis. Proc. Natl. Acad. Sci. U.S.A. 98, 5619–5624 (2001).
29.
B. T. Chen, K. A. Moran, M. V. Avshalumov, M. E. Rice, Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca channels contrasted with strong regulation of axonal dopamine release. J. Neurochem. 96, 645–655 (2006).
30.
K. S. Park, D. P. Mohapatra, H. Misonou, J. S. Trimmer, Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science 313, 976–979 (2006).
31.
H. Misonou, M. Menegola, D. P. Mohapatra, L. K. Guy, K. S. Park, J. S. Trimmer, Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation. J. Neurosci. 26, 13505–13514 (2006).
32.
K. S. Park, D. P. Mohapatra, J. S. Trimmer, Proteomic analyses of Kv2.1 channel phosphorylation sites determining cell background specific differences in function. Channels 1, 59–61 (2007).
33.
G. Shi, A. K. Kleinklaus, N. V. Marrion, J. S. Trimmer, Properties of Kv2.1 K+ channels expressed in transfected mammalian cells. J. Biol. Chem. 269, 23204–23211 (1994).
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Volume 2007 | Issue 393
July 2007
July 2007
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Cited by
- Signal integration at the level of ion channel and exocytotic function in pancreatic β-cells, American Journal of Physiology-Endocrinology and Metabolism, 301, 6, (E1065-E1069), (2011).https://doi.org/10.1152/ajpendo.00426.2011
- Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells, Journal of Cell Science, 123, 11, (1940-1947), (2010).https://doi.org/10.1242/jcs.063719
- Voltage-gated Potassium Channel as a Facilitator of Exocytosis, Annals of the New York Academy of Sciences, 1152, 1, (87-92), (2009).https://doi.org/10.1111/j.1749-6632.2008.03997.x
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