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

• DOI: 10.1073/pnas.1416544112
• Publication Date: 2015-01-01T03:20:09Z
• Authors: Paul M. Jenkins; Namsoo Kim; Steven L. Jones; Wei Chou Tseng; Tatyana M. Svitkina; Henry H. Yin; Vann Bennett
• Keywords: Ankyrins; Mice, Knockout; 0303 health sciences; Action Potentials; Exons; Axons; Protein Structure, Tertiary; Rats; 3. Good health; Evolution, Molecular; Mice; 03 medical and health sciences; Mutation; Ranvier's Nodes; Animals; Signal Transduction

Significance Excitable axonal membrane microdomains are unique features of vertebrate nervous systems that are required for normal neuronal signaling and are involved in human neurological disorders. Ankyrin-G is a critical adaptor protein that acquired a giant exon early in vertebrate evolution, resulting in a new nervous system-specific polypeptide that is a master organizer of axonal excitable membranes. Giant ankyrin-G–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 ankyrin-G thus was a transformative innovation in evolution of the vertebrate nervous system that now is a potential target in neurodevelopmental disorders.