ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity.

Published

Journal Article

Giant ankyrin-B (ankB) is a neurospecific alternatively spliced variant of ANK2, a high-confidence autism spectrum disorder (ASD) gene. We report that a mouse model for human ASD mutation of giant ankB exhibits increased axonal branching in cultured neurons with ectopic CNS axon connectivity, as well as with a transient increase in excitatory synapses during postnatal development. We elucidate a mechanism normally limiting axon branching, whereby giant ankB localizes to periodic axonal plasma membrane domains through L1 cell-adhesion molecule protein, where it couples microtubules to the plasma membrane and prevents microtubule entry into nascent axon branches. Giant ankB mutation or deficiency results in a dominantly inherited impairment in selected communicative and social behaviors combined with superior executive function. Thus, gain of axon branching due to giant ankB-deficiency/mutation is a candidate cellular mechanism to explain aberrant structural connectivity and penetrant behavioral consequences in mice as well as humans bearing ASD-related ANK2 mutations.

Full Text

Duke Authors

Cited Authors

  • Yang, R; Walder-Christensen, KK; Kim, N; Wu, D; Lorenzo, DN; Badea, A; Jiang, Y-H; Yin, HH; Wetsel, WC; Bennett, V

Published Date

  • July 23, 2019

Published In

Volume / Issue

  • 116 / 30

Start / End Page

  • 15262 - 15271

PubMed ID

  • 31285321

Pubmed Central ID

  • 31285321

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1904348116

Language

  • eng

Conference Location

  • United States