Giant ankyrin-G stabilizes somatodendritic GABAergic synapses through opposing endocytosis of GABAA receptors

Wei Chou Tseng, Paul M. Jenkins, Masashi Tanaka, Richard Mooney, Vann Bennett

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

GABAA-receptor-based interneuron circuitry is essential for higher order function of the human nervous system and is implicated in schizophrenia, depression, anxiety disorders, and autism. Here we demonstrate that giant ankyrin-G (480-kDa ankyrin-G) promotes stability of somatodendritic GABAergic synapses in vitro and in vivo. Moreover, giant ankyrin-G forms developmentally regulated and cell-type-specific micron-scale domains within extrasynaptic somatodendritic plasma membranes of pyramidal neurons. We further find that giant ankyrin-G promotes GABAergic synapse stability through opposing endocytosis of GABAA receptors, and requires a newly described interaction with GABARAP, a GABAA receptor-associated protein. We thus present a new mechanism for stabilization of GABAergic interneuron synapses and micron-scale organization of extrasynaptic membrane that provides a rationale for studies linking ankyrin-G genetic variation with psychiatric disease and abnormal neurodevelopment.

Original languageEnglish
Pages (from-to)1214-1219
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number4
DOIs
Publication statusPublished - 2015 Jan 27
Externally publishedYes

Keywords

  • Extrasynaptic membrane
  • GABA receptor endocytosis
  • GABAergic synapses
  • GABARAP
  • Giant ankyrin-G

ASJC Scopus subject areas

  • General

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