JMY powers dendritogenesis and is regulated by CaM revealing a general, critical principle in neuromorphogenesis

Local calcium signals and formation of actin filaments help to steer and power neuronal morphology development and plasticity. Yet, responsible actin nucleators and their linkage to calcium transients largely remained elusive. Here, we identify the WH2 domain-based actin nucleator JMY as target of the calcium sensor calmodulin, reveal that JMY is critical for dendritic arbor formation and unravel that JMY's molecular mechanisms employed in dendritic arborization are depended on Arp2/3 complex interaction, Arp2/3 complex activity and functionality of JMY's WH2 domains, i.e. on JMY's abilities to promote actin filament formation. We furthermore demonstrate that Ca²⁺/calmodulin association regulates the G-actin loading of JMY's first WH2 domain. Consistently, JMY's functions in neuromorphogenesis rely on proper Ca²⁺/calmodulin signaling and on the first WH2 domain. These findings establish Ca²⁺/calmodulin signaling as an important, more widely used, but multifaceted mechanism of tight control of actin nucleators powering dendritic branch formation-a key aspect in neuronal network development in the brain.