Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 300 (5628): 2091-2094

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

A Targeting Motif Involved in Sodium Channel Clustering at the Axonal Initial Segment

Juan José Garrido, Pierre Giraud, Edmond Carlier, Fanny Fernandes, Anissa Moussif, Marie-Pierre Fache, Dominique Debanne, Bénédicte Dargent*

Abstract: The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Nav1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocampal neurons. Expression of a soluble Nav1.2II-III linker protein led to the disorganization of endogenous sodium channels. The motif was sufficient to redirect a somatodendritic potassium channel to the axonal initial segment, a process involving association with ankyrin G. Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity.

Institut National de la Santé et de la Recherche Médicale Unité 464, Institut Jean Roche, Université de la Méditerranée, Faculté de Médecine Secteur-Nord, Boulevard P. Dramard, 13916 Marseille Cedex 20, France.

Back to Top

Note added in proof: During revision of this report, Lemaillet et al. (31) identified a conserved ankyrin-binding motif located within the AIS motif.

* To whom correspondence should be addressed. E-mail: dargent.b{at}jean-roche.univ-mrs.fr

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments.
S. L. Jones, F. Korobova, and T. Svitkina (2014)
J. Cell Biol. 205, 67-81
   Abstract »    Full Text »    PDF »
SRF Phosphorylation by Glycogen Synthase Kinase-3 Promotes Axon Growth in Hippocampal Neurons.
C. L. Li, A. Sathyamurthy, A. Oldenborg, D. Tank, and N. Ramanan (2014)
J. Neurosci. 34, 4027-4042
   Abstract »    Full Text »    PDF »
ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury.
A. del Puerto, L. Fronzaroli-Molinieres, M. J. Perez-Alvarez, P. Giraud, E. Carlier, F. Wandosell, D. Debanne, and J. J. Garrido (2014)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Activity-Dependent and Activity-Independent Development of the Axon Initial Segment.
H. Kuba, R. Adachi, and H. Ohmori (2014)
J. Neurosci. 34, 3443-3453
   Abstract »    Full Text »    PDF »
Ankyrin-B Regulates Cav2.1 and Cav2.2 Channel Expression and Targeting.
C. F. Kline, J. Scott, J. Curran, T. J. Hund, and P. J. Mohler (2014)
J. Biol. Chem. 289, 5285-5295
   Abstract »    Full Text »    PDF »
Silencing of the Tandem Pore Domain Halothane-inhibited K+ Channel 2 (THIK2) Relies on Combined Intracellular Retention and Low Intrinsic Activity at the Plasma Membrane.
F. C. Chatelain, D. Bichet, S. Feliciangeli, M.-M. Larroque, V. M. Braud, D. Douguet, and F. Lesage (2013)
J. Biol. Chem. 288, 35081-35092
   Abstract »    Full Text »    PDF »
Membrane domain organization of myelinated axons requires {beta}II spectrin.
C. Zhang, K. Susuki, D. R. Zollinger, J. L. Dupree, and M. N. Rasband (2013)
J. Cell Biol. 203, 437-443
   Abstract »    Full Text »    PDF »
Na+ Channel-Dependent Recruitment of Nav{beta}4 to Axon Initial Segments and Nodes of Ranvier.
S. A. Buffington and M. N. Rasband (2013)
J. Neurosci. 33, 6191-6202
   Abstract »    Full Text »    PDF »
Aberrant sodium channel activity in the complex seizure disorder of Celf4 mutant mice.
W. Sun, J. L. Wagnon, C. L. Mahaffey, M. Briese, J. Ule, and W. N. Frankel (2013)
J. Physiol. 591, 241-255
   Abstract »    Full Text »    PDF »
Colocalization of {alpha}-actinin and Synaptopodin in the Pyramidal Cell Axon Initial Segment.
D. Sanchez-Ponce, L. Blazquez-Llorca, J. DeFelipe, J. J. Garrido, and A. Munoz (2012)
Cereb Cortex 22, 1648-1661
   Abstract »    Full Text »    PDF »
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier.
A. Gasser, T. S.-Y. Ho, X. Cheng, K.-J. Chang, S. G. Waxman, M. N. Rasband, and S. D. Dib-Hajj (2012)
J. Neurosci. 32, 7232-7243
   Abstract »    Full Text »    PDF »
Alterations in Intrinsic Membrane Properties and the Axon Initial Segment in a Mouse Model of Angelman Syndrome.
H. Kaphzan, S. A. Buffington, J. I. Jung, M. N. Rasband, and E. Klann (2011)
J. Neurosci. 31, 17637-17648
   Abstract »    Full Text »    PDF »
Short- and Long-Term Plasticity at the Axon Initial Segment.
M. S. Grubb, Y. Shu, H. Kuba, M. N. Rasband, V. C. Wimmer, and K. J. Bender (2011)
J. Neurosci. 31, 16049-16055
   Abstract »    Full Text »    PDF »
Action Potential Generation at an Axon Initial Segment-Like Process in the Axonless Retinal AII Amacrine Cell.
C. Wu, E. Ivanova, J. Cui, Q. Lu, and Z.-H. Pan (2011)
J. Neurosci. 31, 14654-14659
   Abstract »    Full Text »    PDF »
Defects in Ankyrin-Based Membrane Protein Targeting Pathways Underlie Atrial Fibrillation.
S. R. Cunha, T. J. Hund, S. Hashemi, N. Voigt, N. Li, P. Wright, O. Koval, J. Li, H. Gudmundsson, R. J. Gumina, et al. (2011)
Circulation 124, 1212-1222
   Abstract »    Full Text »    PDF »
Endocytosis of the Glutamate Receptor Subunit GluK3 Controls Polarized Trafficking.
D. Huyghe, J. Veran, V. F. Labrousse, D. Perrais, C. Mulle, and F. Coussen (2011)
J. Neurosci. 31, 11645-11654
   Abstract »    Full Text »    PDF »
Engineering Light-Regulated Ion Channels.
D. L. Fortin, T. W. Dunn, and R. H. Kramer (2011)
Cold Spring Harb Protoc 2011, pdb.top112
   Abstract »    Full Text »    PDF »
End-binding proteins EB3 and EB1 link microtubules to ankyrin G in the axon initial segment.
C. Leterrier, H. Vacher, M.-P. Fache, S. A. d'Ortoli, F. Castets, A. Autillo-Touati, and B. Dargent (2011)
PNAS 108, 8826-8831
   Abstract »    Full Text »    PDF »
Axon Physiology.
D. Debanne, E. Campanac, A. Bialowas, E. Carlier, and G. Alcaraz (2011)
Physiol Rev 91, 555-602
   Abstract »    Full Text »    PDF »
The C-terminal domain of {beta}IV-spectrin is crucial for KCNQ2 aggregation and excitability at nodes of Ranvier.
J. J. Devaux (2010)
J. Physiol. 588, 4719-4730
   Abstract »    Full Text »    PDF »
Ankyrin G restricts ion channel diffusion at the axonal initial segment before the establishment of the diffusion barrier.
A. Brachet, C. Leterrier, M. Irondelle, M.-P. Fache, V. Racine, J.-B. Sibarita, D. Choquet, and B. Dargent (2010)
J. Cell Biol. 191, 383-395
   Abstract »    Full Text »    PDF »
Two Nedd4-binding Motifs Underlie Modulation of Sodium Channel Nav1.6 by p38 MAPK.
A. Gasser, X. Cheng, E. S. Gilmore, L. Tyrrell, S. G. Waxman, and S. D. Dib-Hajj (2010)
J. Biol. Chem. 285, 26149-26161
   Abstract »    Full Text »    PDF »
Membrane Domains Based on Ankyrin and Spectrin Associated with Cell-Cell Interactions.
V. Bennett and J. Healy (2009)
Cold Spring Harb Perspect Biol 1, a003012
   Abstract »    Full Text »    PDF »
Disruption of the Axon Initial Segment Cytoskeleton Is a New Mechanism for Neuronal Injury.
D. P. Schafer, S. Jha, F. Liu, T. Akella, L. D. McCullough, and M. N. Rasband (2009)
J. Neurosci. 29, 13242-13254
   Abstract »    Full Text »    PDF »
Dual role of KATP channel C-terminal motif in membrane targeting and metabolic regulation.
C. F. Kline, H. T. Kurata, T. J. Hund, S. R. Cunha, O. M. Koval, P. J. Wright, M. Christensen, M. E. Anderson, C. G. Nichols, and P. J. Mohler (2009)
PNAS 106, 16669-16674
   Abstract »    Full Text »    PDF »
Axonal targeting of Caspr2 in hippocampal neurons via selective somatodendritic endocytosis.
C. Bel, K. Oguievetskaia, C. Pitaval, L. Goutebroze, and C. Faivre-Sarrailh (2009)
J. Cell Sci. 122, 3403-3413
   Abstract »    Full Text »    PDF »
Multiple Molecular Interactions Determine the Clustering of Caspr2 and Kv1 Channels in Myelinated Axons.
I. Horresh, S. Poliak, S. Grant, D. Bredt, M. N. Rasband, and E. Peles (2008)
J. Neurosci. 28, 14213-14222
   Abstract »    Full Text »    PDF »
Na+ channels get anchored...with a little help.
M. N. Rasband (2008)
J. Cell Biol. 183, 975-977
   Abstract »    Full Text »    PDF »
Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G.
A. Brechet, M.-P. Fache, A. Brachet, G. Ferracci, A. Baude, M. Irondelle, S. Pereira, C. Leterrier, and B. Dargent (2008)
J. Cell Biol. 183, 1101-1114
   Abstract »    Full Text »    PDF »
AnkyrinG is required for maintenance of the axon initial segment and neuronal polarity.
K. L. Hedstrom, Y. Ogawa, and M. N. Rasband (2008)
J. Cell Biol. 183, 635-640
   Abstract »    Full Text »    PDF »
Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons.
H. Vacher, D. P. Mohapatra, and J. S. Trimmer (2008)
Physiol Rev 88, 1407-1447
   Abstract »    Full Text »    PDF »
Role of Axonal NaV1.6 Sodium Channels in Action Potential Initiation of CA1 Pyramidal Neurons.
M. Royeck, M.-T. Horstmann, S. Remy, M. Reitze, Y. Yaari, and H. Beck (2008)
J Neurophysiol 100, 2361-2380
   Abstract »    Full Text »    PDF »
Schwannomin-Interacting Protein-1 Isoform IQCJ-SCHIP-1 Is a Late Component of Nodes of Ranvier and Axon Initial Segments.
P.-M. Martin, M. Carnaud, G. G. del Cano, M. Irondelle, T. Irinopoulou, J.-A. Girault, B. Dargent, and L. Goutebroze (2008)
J. Neurosci. 28, 6111-6117
   Abstract »    Full Text »    PDF »
Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2.
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 »
Pathway selection to the axon depends on multiple targeting signals in NgCAM.
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 »
Spectrin and Ankyrin-Based Cytoskeletons at Polarized Domains in Myelinated Axons.
K. Susuki and M. N. Rasband (2008)
Experimental Biology and Medicine 233, 394-400
   Abstract »    Full Text »    PDF »
The C-terminus of Kv7 channels: a multifunctional module.
Y. Haitin and B. Attali (2008)
J. Physiol. 586, 1803-1810
   Abstract »    Full Text »    PDF »
Being there: cellular targeting of voltage-gated sodium channels in the heart.
V. Bennett and J. Healy (2008)
J. Cell Biol. 180, 13-15
   Abstract »    Full Text »    PDF »
Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway.
J. S. Lowe, O. Palygin, N. Bhasin, T. J. Hund, P. A. Boyden, E. Shibata, M. E. Anderson, and P. J. Mohler (2008)
J. Cell Biol. 180, 173-186
   Abstract »    Full Text »    PDF »
The Axon Dendrite Targeting of Kv3 (Shaw) Channels Is Determined by a Targeting Motif That Associates with the T1 Domain and Ankyrin G.
M. Xu, R. Cao, R. Xiao, M. X. Zhu, and C. Gu (2007)
J. Neurosci. 27, 14158-14170
   Abstract »    Full Text »    PDF »
The FGF14F145S Mutation Disrupts the Interaction of FGF14 with Voltage-Gated Na+ Channels and Impairs Neuronal Excitability.
F. Laezza, B. R. Gerber, J.-Y. Lou, M. A. Kozel, H. Hartman, A. Marie Craig, D. M. Ornitz, and J. M. Nerbonne (2007)
J. Neurosci. 27, 12033-12044
   Abstract »    Full Text »    PDF »
Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions.
P. J. Mohler and X. H. T. Wehrens (2007)
Physiology 22, 342-350
   Abstract »    Full Text »    PDF »
Ankyrin-G Is a Molecular Partner of E-cadherin in Epithelial Cells and Early Embryos.
K. Kizhatil, J. Q. Davis, L. Davis, J. Hoffman, B. L. M. Hogan, and V. Bennett (2007)
J. Biol. Chem. 282, 26552-26561
   Abstract »    Full Text »    PDF »
Neurofascin assembles a specialized extracellular matrix at the axon initial segment.
K. L. Hedstrom, X. Xu, Y. Ogawa, R. Frischknecht, C. I. Seidenbecher, P. Shrager, and M. N. Rasband (2007)
J. Cell Biol. 178, 875-886
   Abstract »    Full Text »    PDF »
Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms.
Y. Dzhashiashvili, Y. Zhang, J. Galinska, I. Lam, M. Grumet, and J. L. Salzer (2007)
J. Cell Biol. 177, 857-870
   Abstract »    Full Text »    PDF »
Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation.
I. Ogiwara, H. Miyamoto, N. Morita, N. Atapour, E. Mazaki, I. Inoue, T. Takeuchi, S. Itohara, Y. Yanagawa, K. Obata, et al. (2007)
J. Neurosci. 27, 5903-5914
   Abstract »    Full Text »    PDF »
Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment.
H. B. Rasmussen, C. Frokjaer-Jensen, C. S. Jensen, H. S. Jensen, N. K. Jorgensen, H. Misonou, J. S. Trimmer, S.-P. Olesen, and N. Schmitt (2007)
J. Cell Sci. 120, 953-963
   Abstract »    Full Text »    PDF »
{beta}IV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG.
Y. Yang, Y. Ogawa, K. L. Hedstrom, and M. N. Rasband (2007)
J. Cell Biol. 176, 509-519
   Abstract »    Full Text »    PDF »
Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron-Glia Cell Adhesion Molecule.
T. Boiko, M. Vakulenko, H. Ewers, C. C. Yap, C. Norden, and B. Winckler (2007)
J. Neurosci. 27, 590-603
   Abstract »    Full Text »    PDF »
Neuron-glia communication in the control of oligodendrocyte function and myelin biogenesis.
M. Simons and K. Trajkovic (2006)
J. Cell Sci. 119, 4381-4389
   Abstract »    Full Text »    PDF »
Identification of sequence motifs that target neuronal nicotinic receptors to dendrites and axons..
J. Xu, Y. Zhu, and S. F. Heinemann (2006)
J. Neurosci. 26, 9780-9793
   Abstract »    Full Text »    PDF »
Ankyrin-G Regulates Inactivation Gating of the Neuronal Sodium Channel, Nav1.6.
E. Shirahata, H. Iwasaki, M. Takagi, C. Lin, V. Bennett, Y. Okamura, and K. Hayasaka (2006)
J Neurophysiol 96, 1347-1357
   Abstract »    Full Text »    PDF »
Cardiac ankyrins: Essential components for development and maintenance of excitable membrane domains in heart.
S. R. Cunha and P. J. Mohler (2006)
Cardiovasc Res 71, 22-29
   Abstract »    Full Text »    PDF »
Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton..
Y. Ogawa, D. P. Schafer, I. Horresh, V. Bar, K. Hales, Y. Yang, K. Susuki, E. Peles, M. C. Stankewich, and M. N. Rasband (2006)
J. Neurosci. 26, 5230-5239
   Abstract »    Full Text »    PDF »
A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon..
Z. Pan, T. Kao, Z. Horvath, J. Lemos, J.-Y. Sul, S. D. Cranstoun, V. Bennett, S. S. Scherer, and E. C. Cooper (2006)
J. Neurosci. 26, 2599-2613
   Abstract »    Full Text »    PDF »
A Role for Kif17 in Transport of Kv4.2.
P.-J. Chu, J. F. Rivera, and D. B. Arnold (2006)
J. Biol. Chem. 281, 365-373
   Abstract »    Full Text »    PDF »
Differential targeting and functional specialization of sodium channels in cultured cerebellar granule cells.
N. Osorio, G. Alcaraz, F. Padilla, F. Couraud, P. Delmas, and M. Crest (2005)
J. Physiol. 569, 801-816
   Abstract »    Full Text »    PDF »
Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels.
J.-Y. Lou, F. Laezza, B. R. Gerber, M. Xiao, K. A. Yamada, H. Hartmann, A. M. Craig, J. M. Nerbonne, and D. M. Ornitz (2005)
J. Physiol. 569, 179-193
   Abstract »    Full Text »    PDF »
Where Is the Spike Generator of the Cochlear Nerve? Voltage-Gated Sodium Channels in the Mouse Cochlea.
W. A. Hossain, S. D. Antic, Y. Yang, M. N. Rasband, and D. K. Morest (2005)
J. Neurosci. 25, 6857-6868
   Abstract »    Full Text »    PDF »
RNA interference rescue by bacterial artificial chromosome transgenesis in mammalian tissue culture cells.
R. Kittler, L. Pelletier, C. Ma, I. Poser, S. Fischer, A. A. Hyman, and F. Buchholz (2005)
PNAS 102, 2396-2401
   Abstract »    Full Text »    PDF »
Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.
P. J. Mohler, I. Rivolta, C. Napolitano, G. LeMaillet, S. Lambert, S. G. Priori, and V. Bennett (2004)
PNAS 101, 17533-17538
   Abstract »    Full Text »    PDF »
Endocytotic elimination and domain-selective tethering constitute a potential mechanism of protein segregation at the axonal initial segment.
M.-P. Fache, A. Moussif, F. Fernandes, P. Giraud, J. J. Garrido, and B. Dargent (2004)
J. Cell Biol. 166, 571-578
   Abstract »    Full Text »    PDF »
A cardiac arrhythmia syndrome caused by loss of ankyrin-B function.
P. J. Mohler, I. Splawski, C. Napolitano, G. Bottelli, L. Sharpe, K. Timothy, S. G. Priori, M. T. Keating, and V. Bennett (2004)
PNAS 101, 9137-9142
   Abstract »    Full Text »    PDF »
Sodium Channel {beta}1 Subunit-mediated Modulation of Nav1.2 Currents and Cell Surface Density Is Dependent on Interactions with Contactin and Ankyrin.
D. P. McEwen, L. S. Meadows, C. Chen, V. Thyagarajan, and L. L. Isom (2004)
J. Biol. Chem. 279, 16044-16049
   Abstract »    Full Text »    PDF »
The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells.
S. Q. Wang, M. D. Stern, E. Rios, and H. Cheng (2004)
PNAS 101, 3979-3984
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882