Faculty Opinions recommendation of Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments.

Author(s):  
Stanley Froehner
2001 ◽  
Vol 155 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Scott M. Jenkins ◽  
Vann Bennett

The axon initial segment is an excitable membrane highly enriched in voltage-gated sodium channels that integrates neuronal inputs and initiates action potentials. This study identifies Nav1.6 as the voltage-gated sodium channel isoform at mature Purkinje neuron initial segments and reports an essential role for ankyrin-G in coordinating the physiological assembly of Nav1.6, βIV spectrin, and the L1 cell adhesion molecules (L1 CAMs) neurofascin and NrCAM at initial segments of cerebellar Purkinje neurons. Ankyrin-G and βIV spectrin appear at axon initial segments by postnatal day 2, whereas L1 CAMs and Nav1.6 are not fully assembled at continuous high density along axon initial segments until postnatal day 9. L1 CAMs and Nav1.6 therefore do not initiate protein assembly at initial segments. βIV spectrin, Nav1.6, and L1 CAMs are not clustered in adult Purkinje neuron initial segments of mice lacking cerebellar ankyrin-G. These results support the conclusion that ankyrin-G coordinates the physiological assembly of a protein complex containing transmembrane adhesion molecules, voltage-gated sodium channels, and the spectrin membrane skeleton at axon initial segments.


2002 ◽  
Vol 156 (2) ◽  
pp. 337-348 ◽  
Author(s):  
Masayuki Komada ◽  
Philippe Soriano

β-Spectrin and ankyrin are major components of the membrane cytoskeleton. We have generated mice carrying a null mutation in the βIV-spectrin gene using gene trapping in embryonic stem cells. Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. βIV-spectrin expression is mostly restricted to neurons, where it colocalizes with and binds to ankyrin-G at axon initial segments (AISs) and nodes of Ranvier (NR). In βIV-spectrin–null neurons, neither ankyrin-G nor voltage-gated sodium channels (VGSC) are correctly clustered at these sites, suggesting that impaired action potential caused by mislocalization of VGSC leads to the phenotype. Conversely, in ankyrin-G–null neurons, βIV-spectrin is not localized to these sites. These results indicate that βIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR.


2002 ◽  
Vol 323 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Thomas Kretschmer ◽  
John D. England ◽  
Leo T. Happel ◽  
Z.P. Liu ◽  
Carol L. Thouron ◽  
...  

Author(s):  
Zhi-mei Li ◽  
Li-xia Chen ◽  
Hua Li

The article “Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go?”, written by Zhi-mei LI, Li-xia CHEN, Hua LI, was originally published electronically on the publisher’s internet portal on December 2019 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The original article has been corrected.Corresponding authors: Li-xia CHEN, Hua LI


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