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

## TL;DR

The study shows how calcium signaling controls the actin nucleator JMY, which is essential for forming dendrites in neurons.

## Contribution

The paper identifies JMY as a calmodulin target and reveals its role in dendritic arborization through actin nucleation.

## Key findings

- JMY is a critical actin nucleator for dendritic arbor formation.
- JMY's function depends on Arp2/3 complex interaction and its WH2 domains.
- Ca2+/calmodulin signaling regulates JMY's G-actin loading and dendritic branch formation.

## Abstract

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.

Identification of the actin nucleator JMY as calmodulin (CaM) target, of JMY’s critical role in dendritic arborization and of the molecular mechanisms used by JMY establishes Ca2+/CaM signaling as key principle for actin-driven neuromorphogenesis.