Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG

Xiaoyun Ding, Yu Wu, Anna Vainshtein, Victoria Rodriguez, Emily Ricco, James T. Okoh, Yanhong Liu, Daniel C. Kraushaar, Elior Peles, Matthew N. Rasband

Research output: Contribution to journalArticlepeer-review

Abstract

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In addition, these mice exhibit significant histological, electrophysiological, and behavioral pathophysiologies. Unbiased translatomic profiling reveals potential compensatory machineries. These results highlight the functions of glial AnkG in maintaining proper axoglial interactions throughout aging and suggest a contribution of glial AnkG to neuropsychiatric disorders.

Original languageEnglish
Article number10865
JournalNature Communications
Volume15
DOIs
StatePublished - 30 Dec 2024

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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