Program in Developmental Biology, Baylor College of Medicine, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States
Yuki Ogawa
Department of Neuroscience, Baylor College of Medicine, Houston, United States
Department of Neuroscience, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
Department of Neuroscience, Baylor College of Medicine, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States
Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv+ fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying β1 spectrin-based cytoskeleton.