The N-Ank protein Ankrd24 shapes neurons and couples to syndapin and the F-actin promoter Cobl-like

Proper neuromorphogenesis is pivotal for neuronal network formation and brain function. The underlying cell biological tasks are complex, as they include both remodeling of membrane topologies and of cytoskeletal structures. Yet, mechanisms coordinating these two different cell biological functions are largely unknown. Here, we molecularly and functionally characterize ankyrin repeat domain-containing protein 24 (Ankrd24) and demonstrate that this ankyrin-repeat protein is able to interact with and bend membranes and mechanistically and functionally belongs to the recently proposed N-Ank superfamily. Mutational analyses revealed that the N-Ank functions of Ankrd24 are indispensable for Ankrd24’s role in neuromorphogenesis. Ankrd24 furthermore physically cooperated with the F-BAR domain protein syndapin I (PACSIN1) and with Cobl-like (Cobll1), a protein promoting actin filament formation, by ternary complex formation. Both partners were critical for Ankrd24-mediated dendritic arborization. This identified Ankrd24 as critical part of a larger, coordinated effort in inducing new dendritic branches. Our work thereby sheds light on the molecular mechanisms underlying the complex task of proper neuronal arbor development.