The functional organization and assembly of the axon initial segment

Current Opinion in Neurobiology

Volumn 18, Issue 3, 2008, Pages 307-313

  Ogawa, Yasuhiro ^a   Rasband, Matthew N ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ADHESION MOLECULE; CYTOSKELETON PROTEIN; ION CHANNEL; SCAFFOLD PROTEIN;

ACTION POTENTIAL; EXTRACELLULAR MATRIX; NERVE CELL MEMBRANE POTENTIAL; NERVE CELL PLASTICITY; NERVE ENDING; NERVE EXCITABILITY; NERVE FIBER; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANVIER NODE; REVIEW;

ACTION POTENTIALS; ANIMALS; AXONS; CELL ADHESION MOLECULES; CYTOSKELETON; EXTRACELLULAR MATRIX; NERVE TISSUE PROTEINS; PRESYNAPTIC TERMINALS;

EID: 53949093474     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.conb.2008.08.008     Document Type: Review

References (42)

1. + channels and ankG.
2. Hedstrom K.L., and Rasband M.N. Intrinsic and extrinsic determinants of ion channel localization in neurons. J Neurochem 98 (2006) 1345-1352
3. Sherman D.L., Tait S., Melrose S., Johnson R., Zonta B., Court F.A., Macklin W.B., Meek S., Smith A.J., Cottrell D.F., et al. Neurofascins are required to establish axonal domains for saltatory conduction. Neuron 48 (2005) 737-742
4. Eshed Y., Feinberg K., Poliak S., Sabanay H., Sarig-Nadir O., Spiegel I., Bermingham Jr. J.R., and Peles E. Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier. Neuron 47 (2005) 215-229
5. Ogiwara I., Miyamoto H., Morita N., Atapour N., Mazaki E., Inoue I., Takeuchi T., Itohara S., Yanagawa Y., Obata K., et al. Na(v)1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 27 (2007) 5903-5914. This paper demonstrates that Nav1.1 channels are specifically enriched at the AIS of cortical interneurons. Using a Nav1.1 knockin mouse mutant to mimic a human form of epilepsy, the authors show that the disruption of Nav1.1 channels alters neuronal excitability. The authors propose that the disruption of these inhibitory circuits might account for the epileptic seizures.
6. Alessandri-Haber N., Alcaraz G., Deleuze C., Jullien F., Manrique C., Couraud F., Crest M., and Giraud P. Molecular determinants of emerging excitability in rat embryonic motoneurons. J Physiol 541 (2002) 25-39
7. Boiko T., Van Wart A., Caldwell J.H., Levinson S.R., Trimmer J.S., and Matthews G. Functional specialization of the axon initial segment by isoform-specific sodium channel targeting. J Neurosci 23 (2003) 2306-2313
8. Yang Y., Ogawa Y., Hedstrom K.L., and Rasband M.N. {beta}IV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. J Cell Biol 176 (2007) 509-519. The authors demonstrate that the 15th spectrin repeat of βIV spectrin binds to ankG. They show that ankG recruits βIV spectrin to the nodes of Ranvier and the AIS. This is the first paper to demonstrate the nodal targeting of recombinant proteins both in vivo and in vitro.
9. Duflocq A., Le Bras B., Bullier E., Couraud F., and Davenne M. Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments. Mol Cell Neurosci 39 (2008) 180-192
10. Van Wart A., Trimmer J.S., and Matthews G. Polarized distribution of ion channels within microdomains of the axon initial segment. J Comp Neurol 500 (2007) 339-352
11. Grieco T.M., Malhotra J.D., Chen C., Isom L.L., and Raman I.M. Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current. Neuron 45 (2005) 233-244
12. + channels and impairs neuronal excitability. J Neurosci 27 (2007) 12033-12044
13. Pan Z., Kao T., Horvath Z., Lemos J., Sul J.-Y., Cranstoun S.D., Bennett M.V., Scherer S.S., and Cooper E.C. A common ankyrin-G-based mechanism retains KCNQ and Nav channels at electrically active domains of the axon. J Neurosci 26 (2006) 2599-2613
14. Shah M.M., Migliore M., Valencia I., Cooper E.C., and Brown D.A. Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci U S A 105 (2008) 7869-7874
15. Jentsch T.J. Neuronal KCNQ potassium channels: physiology and role in disease. Nat Rev Neurosci 1 (2000) 21-30
16. Johnston J., Griffin S.J., Baker C., Skrzypiec A., Chernova T., and Forsythe I.D. Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in MNTB neurones. J Physiol 586 (2008) 3493-3509
17. Inda M.C., Defelipe J., and Munoz A. Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells. Proc Natl Acad Sci U S A 103 (2006) 2920-2925
18. Kuba H., Ishii T.M., and Ohmori H. Axonal site of spike initiation enhances auditory coincidence detection. Nature 444 (2006) 1069-1072. In this remarkable paper, the authors demonstrate that the location of the AIS is precisely controlled to regulate neuronal activity and function. It is one of the first papers to demonstrate the functional plasticity of the AIS.
19. Ogawa Y., Horresh I., Trimmer J.S., Bredt D.S., Peles E., and Rasband M.N. Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2. J Neurosci 28 (2008) 5731-5739. This paper shows that the scaffolding protein PSD-93, but not Caspr2, is required for the AIS clustering of Kv1 channels. This is distinct from the juxtaparanodes of myelinated axons, demonstrating that although the AIS and nodal regions share a common molecular organization, each uses distinct mechanisms to initiate channel clustering.
20. Kole M.H., Letzkus J.J., and Stuart G.J. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron 55 (2007) 633-647. The authors show that Kv1 channels at the AIS play important physiological roles in regulating the duration of action potentials. This paper revealed a previously unappreciated role for Kv1 channels at the AIS.
21. + channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron 58 (2008) 387-400. This study shows that Kv1 channels at the AIS directly regulate the firing rate of these interneurons. Thus, the unique complements of ion channels expressed in specific cell types could dramatically influence the overall nervous system function.
22. Hedstrom K.L., Xu X., Ogawa Y., Frischknecht R., Seidenbecher C.I., Shrager P., and Rasband M.N. Neurofascin assembles a specialized extracellular matrix at the axon initial segment. J Cell Biol 178 (2007) 875-886. Using an shRNA knockdown strategy, the authors silence the expression of AIS CAMs, scaffolds, and ion channels. They show that ankG, rather than NF-186, initiates AIS assembly. This is different from the nodes of Ranvier, pointing to the distinct mechanisms nodes and AIS used to assemble these domains. Finally, they demonstrate that NF-186 interacts with the chondroitin sulfate proteoglycan brevican to assemble the AIS ECM.
23. Strauss K.A., Puffenberger E.G., Huentelman M.J., Gottlieb S., Dobrin S.E., Parod J.M., Stephan D.A., and Morton D.H. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N Engl J Med 354 (2006) 1370-1377
24. Stephan D.A. Unraveling autism. Am J Hum Genet 82 (2008) 7-9
25. + channels by interaction with a family of membrane-associated guanylate kinases. Nature 378 (1995) 85-88
26. Bruckner G., Szeoke S., Pavlica S., Grosche J., and Kacza J. Axon initial segment ensheathed by extracellular matrix in perineuronal nets. Neuroscience 138 (2006) 365-375
27. John N., Krugel H., Frischknecht R., Smalla K.H., Schultz C., Kreutz M.R., Gundelfinger E.D., and Seidenbecher C.I. Brevican-containing perineuronal nets of extracellular matrix in dissociated hippocampal primary cultures. Mol Cell Neurosci 31 (2006) 774-784
28. Schultz C., Konig H.G., Del Turco D., Politi C., Eckert G.P., Ghebremedhin E., Prehn J.H., Kogel D., and Deller T. Coincident enrichment of phosphorylated IkappaBalpha, activated IKK, and phosphorylated p65 in the axon initial segment of neurons. Mol Cell Neurosci 33 (2006) 68-80
29. Sanchez-Ponce D., Tapia M., Munoz A., and Garrido J.J. New role of IKK alpha/beta phosphorylated IkappaB alpha in axon outgrowth and axon initial segment development. Mol Cell Neurosci 37 (2008) 832-844
30. Garver T.D., Ren Q., Tuvia S., and Bennett V. Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin. J Cell Biol 137 (1997) 703-714
31. Lemaillet G., Walker B., and Lambert S. Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits. J Biol Chem 278 (2003) 27333-27339
32. Garrido J.J., Giraud P., Carlier E., Fernandes F., Moussif A., Fache M.P., Debanne D., and Dargent B. A targeting motif involved in sodium channel clustering at the axonal initial segment. Science 300 (2003) 2091-2094
33. Zhou D., Lambert S., Malen P.L., Carpenter S., Boland L.M., and Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 143 (1998) 1295-1304
34. + channel expression. J Neurosci Res 79 (2005) 428-441
35. Komada M., and Soriano P. [Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J Cell Biol 156 (2002) 337-348
36. Yang Y., Lacas-Gervais S., Morest D.K., Solimena M., and Rasband M.N. BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier. J Neurosci 24 (2004) 7230-7240
37. Lacas-Gervais S., Guo J., Strenzke N., Scarfone E., Kolpe M., Jahkel M., De Camilli P., Moser T., Rasband M.N., and Solimena M. BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments. J Cell Biol 166 (2004) 983-990
38. Khirug S., Yamada J., Afzalov R., Voipio J., Khiroug L., and Kaila K. GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1. J Neurosci 28 (2008) 4635-4639
39. Burkarth N., Kriebel M., Kranz E.U., and Volkmer H. Neurofascin regulates the formation of gephyrin clusters and their subsequent translocation to the axon hillock of hippocampal neurons. Mol Cell Neurosci 36 (2007) 59-70
40. + channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162 (2003) 1149-1160
41. Eshed Y., Feinberg K., Carey D.J., and Peles E. Secreted gliomedin is a perinodal matrix component of peripheral nerves. J Cell Biol 177 (2007) 551-562
42. Dzhashiashvili Y., Zhang Y., Galinska J., Lam I., Grumet M., and Salzer J.L. Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms. J Cell Biol 177 (2007) 857-870. The authors use shRNA to silence the expression of ankG in myelinated dorsal root ganglion-Schwann cell cocultures. They demonstrate that NF-186 is recruited to the nodes of Ranvier through extracellular interactions, and that ankG is then recruited by NF-186. The silencing of ankG expression blocks the assembly of Nav channel clusters. This paper provides clear evidence in support of ankG's essential role at PNS nodes of Ranvier.