TY - JOUR T1 - Physical and functional convergence of the autism risk genes <em>Scn2a</em> and <em>Ank2</em> in neocortical pyramidal cell dendrites JF - bioRxiv DO - 10.1101/2022.05.31.494205 SP - 2022.05.31.494205 AU - Andrew D. Nelson AU - Amanda M. Catalfio AU - Julie M. Gupta AU - Lia Min AU - Rene N. Caballero-Floran AU - Kendall P. Dean AU - Carina C. Elvira AU - Kimberly D. Derderian AU - Henry Kyoung AU - Atehsa Sahagun AU - Stephan J. Sanders AU - Kevin J. Bender AU - Paul M. Jenkins Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/06/01/2022.05.31.494205.abstract N2 - Dysfunction in sodium channels and their ankyrin scaffolding partners have both been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). In particular, the genes SCN2A, which encodes the sodium channel NaV1.2, and ANK2, which encodes ankyrin-B, have strong ASD association. Recent studies indicate that ASD-associated haploinsufficiency in Scn2a impairs dendritic excitability and synaptic function in neocortical pyramidal cells, but how NaV1.2 is anchored within dendritic regions is unknown. Here, we show that ankyrin-B is essential for scaffolding NaV1.2 to the dendritic membrane of mouse neocortical neurons, and that haploinsufficiency of Ank2 phenocopies intrinsic dendritic excitability and synaptic deficits observed in Scn2a+/- conditions. Thus, these results establish a direct, convergent link between two major ASD risk genes and reinforce an emerging framework suggesting that neocortical pyramidal cell dendritic dysfunction can be etiological to neurodevelopmental disorder pathophysiology.Competing Interest StatementThe authors have declared no competing interest. ER -