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Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G

Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by... In neurons, generation and propagation of action potentials requires the precise accumulation of sodium channels at the axonal initial segment (AIS) and in the nodes of Ranvier through ankyrin G scaffolding. We found that the ankyrin-binding motif of Na v 1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na v channel interaction with ankyrins. Furthermore, we observed that CK2 is highly enriched at the AIS and the nodes of Ranvier in vivo. An ion channel chimera containing the Na v 1.2 ankyrin-binding motif perturbed endogenous sodium channel accumulation at the AIS, whereas phosphorylation-deficient chimeras did not. Finally, inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. Footnotes Sandrine Pereira's present address is Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 910, Université de la Méditerranée, Faculté de Médecine secteur-Timone, Marseille 13385, France. Abbreviations used in this paper: AIS, axonal initial segment; CK2, protein kinase CK2; CNS, central nervous system; DIV, days in vitro; DMAT, 2-dimethylamino-4,5,6,7-tetrabromo1 H -benzimidazole; MAP2, microtubule-associated protein 2; MBD, membrane-binding domain; MBD-ank, MBD-ankyrin; PNS, peripheral nervous system; SPR, surface plasmon resonance. © 2008 Bréchet et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ). Submitted: 28 May 2008 Accepted: 7 November 2008 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G

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References (55)

Publisher
Rockefeller University Press
Copyright
© 2008 Bréchet et al.
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.200805169
pmid
19064667
Publisher site
See Article on Publisher Site

Abstract

In neurons, generation and propagation of action potentials requires the precise accumulation of sodium channels at the axonal initial segment (AIS) and in the nodes of Ranvier through ankyrin G scaffolding. We found that the ankyrin-binding motif of Na v 1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na v channel interaction with ankyrins. Furthermore, we observed that CK2 is highly enriched at the AIS and the nodes of Ranvier in vivo. An ion channel chimera containing the Na v 1.2 ankyrin-binding motif perturbed endogenous sodium channel accumulation at the AIS, whereas phosphorylation-deficient chimeras did not. Finally, inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. Footnotes Sandrine Pereira's present address is Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 910, Université de la Méditerranée, Faculté de Médecine secteur-Timone, Marseille 13385, France. Abbreviations used in this paper: AIS, axonal initial segment; CK2, protein kinase CK2; CNS, central nervous system; DIV, days in vitro; DMAT, 2-dimethylamino-4,5,6,7-tetrabromo1 H -benzimidazole; MAP2, microtubule-associated protein 2; MBD, membrane-binding domain; MBD-ank, MBD-ankyrin; PNS, peripheral nervous system; SPR, surface plasmon resonance. © 2008 Bréchet et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ). Submitted: 28 May 2008 Accepted: 7 November 2008

Journal

The Journal of Cell Biology – Rockefeller University Press

Published: Dec 15, 2008

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