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Neuron. 2014 Oct 22;84(2):399-415. doi: 10.1016/j.neuron.2014.10.010. Epub 2014 Oct 22.

Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses.

Author information

1
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA.
2
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA.
3
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA.
4
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA.
5
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611 USA. Electronic address: p-penzes@northwestern.edu.

Abstract

Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology. Using superresolution microscopy we find that ankyrin-G forms distinct nanodomain structures within the spine head and neck. At these sites, it modulates mushroom spine structure and function, probably as a perisynaptic scaffold and barrier within the spine neck. Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains, where it differentially regulates NMDA receptor-dependent plasticity. These data implicate subsynaptic nanodomains containing a major psychiatric risk molecule, ankyrin-G, as having location-specific functions and open directions for basic and translational investigation of psychiatric risk molecules.

PMID:
25374361
PMCID:
PMC4223651
DOI:
10.1016/j.neuron.2014.10.010
[Indexed for MEDLINE]
Free PMC Article

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