Details

Autor(en) / Beteiligte

• Smith, Katharine R
• Kopeikina, Katherine J
• Fawcett-Patel, Jessica M
• Leaderbrand, Katherine
• Gao, Ruoqi
• Schürmann, Britta
• Myczek, Kristoffer
• Radulovic, Jelena
• Swanson, Geoffrey T
• Penzes, Peter

Titel

Psychiatric Risk FactorANK3/Ankyrin-G Nanodomains Regulate the Structure and Function of Glutamatergic Synapses

Ist Teil von

• Neuron (Cambridge, Mass.), 2014-10, Vol.84 (2), p.399

Ort / Verlag

Cambridge: Elsevier Limited

Erscheinungsjahr

2014

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in theANK3gene, 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.