TY - JOUR
T1 - Psychiatric Risk Factor ANK3/Ankyrin-G Nanodomains Regulate the Structure and Function of Glutamatergic Synapses
AU - Smith, Katharine R.
AU - Kopeikina, Katherine J.
AU - Fawcett-Patel, Jessica M.
AU - Leaderbrand, Katherine
AU - Gao, Ruoqi
AU - Schürmann, Britta
AU - Myczek, Kristoffer
AU - Radulovic, Jelena
AU - Swanson, Geoffrey T.
AU - Penzes, Peter
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/10/22
Y1 - 2014/10/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908223216&partnerID=8YFLogxK
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U2 - 10.1016/j.neuron.2014.10.010
DO - 10.1016/j.neuron.2014.10.010
M3 - Article
C2 - 25374361
AN - SCOPUS:84908223216
SN - 0896-6273
VL - 84
SP - 399
EP - 415
JO - Neuron
JF - Neuron
IS - 2
ER -