Skip to main content
Journal cover image

Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling.

Publication ,  Journal Article
Jenkins, PM; Kim, N; Jones, SL; Tseng, WC; Svitkina, TM; Yin, HH; Bennett, V
Published in: Proc Natl Acad Sci U S A
January 27, 2015

Axon initial segments (AISs) and nodes of Ranvier are sites of clustering of voltage-gated sodium channels (VGSCs) in nervous systems of jawed vertebrates that facilitate fast long-distance electrical signaling. We demonstrate that proximal axonal polarity as well as assembly of the AIS and normal morphogenesis of nodes of Ranvier all require a heretofore uncharacterized alternatively spliced giant exon of ankyrin-G (AnkG). This exon has sequence similarity to I-connectin/Titin and was acquired after the first round of whole-genome duplication by the ancestral ANK2/ANK3 gene in early vertebrates before development of myelin. The giant exon resulted in a new nervous system-specific 480-kDa polypeptide combining previously known features of ANK repeats and β-spectrin-binding activity with a fibrous domain nearly 150 nm in length. We elucidate previously undescribed functions for giant AnkG, including recruitment of β4 spectrin to the AIS that likely is regulated by phosphorylation, and demonstrate that 480-kDa AnkG is a major component of the AIS membrane "undercoat' imaged by platinum replica electron microscopy. Surprisingly, giant AnkG-knockout neurons completely lacking known AIS components still retain distal axonal polarity and generate action potentials (APs), although with abnormal frequency. Giant AnkG-deficient mice live to weaning and provide a rationale for survival of humans with severe cognitive dysfunction bearing a truncating mutation in the giant exon. The giant exon of AnkG is required for assembly of the AIS and nodes of Ranvier and was a transformative innovation in evolution of the vertebrate nervous system that now is a potential target in neurodevelopmental disorders.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 27, 2015

Volume

112

Issue

4

Start / End Page

957 / 964

Location

United States

Related Subject Headings

  • Signal Transduction
  • Rats
  • Ranvier's Nodes
  • Protein Structure, Tertiary
  • Mutation
  • Mice, Knockout
  • Mice
  • Exons
  • Evolution, Molecular
  • Axons
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jenkins, P. M., Kim, N., Jones, S. L., Tseng, W. C., Svitkina, T. M., Yin, H. H., & Bennett, V. (2015). Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling. Proc Natl Acad Sci U S A, 112(4), 957–964. https://doi.org/10.1073/pnas.1416544112
Jenkins, Paul M., Namsoo Kim, Steven L. Jones, Wei Chou Tseng, Tatyana M. Svitkina, Henry H. Yin, and Vann Bennett. “Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling.Proc Natl Acad Sci U S A 112, no. 4 (January 27, 2015): 957–64. https://doi.org/10.1073/pnas.1416544112.
Jenkins PM, Kim N, Jones SL, Tseng WC, Svitkina TM, Yin HH, et al. Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling. Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):957–64.
Jenkins, Paul M., et al. “Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling.Proc Natl Acad Sci U S A, vol. 112, no. 4, Jan. 2015, pp. 957–64. Pubmed, doi:10.1073/pnas.1416544112.
Jenkins PM, Kim N, Jones SL, Tseng WC, Svitkina TM, Yin HH, Bennett V. Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling. Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):957–964.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 27, 2015

Volume

112

Issue

4

Start / End Page

957 / 964

Location

United States

Related Subject Headings

  • Signal Transduction
  • Rats
  • Ranvier's Nodes
  • Protein Structure, Tertiary
  • Mutation
  • Mice, Knockout
  • Mice
  • Exons
  • Evolution, Molecular
  • Axons