Opposing Roles for the Spectraplakin Short Stop in Stable and Dynamic Dendrites Reveal Divergent DLK Signaling and a Role in Dendrite Regeneration

Dendrites are crucial for neuronal function, but the processes behind their maintenance or regeneration are not well understood. The Drosophila gene short stop (shot) behaves as an actin-microtubule crosslinker during neuronal development. Researchers examined shot's role in dendrite stability and repair in Drosophila sensory neurons.

Shot has contrasting, cell-specific responsibilities in dendrite maintenance: it limits uncontrolled branch growth in simple, stable neurons, while being necessary for dendrite coverage in complex, dynamic neurons. These differing functions are indicated by their distinct localization patterns in stable versus dynamic dendrite arbors.

The absence of shot weakens the microtubule cytoskeleton in stable neurons, and triggers Wallenda/DLK signaling in both stable and dynamic neurons. Wallenda/DLK signaling downstream results in JNK signaling branching between neuron types, with typical basket/JNK activation found only in neurons with stable dendritic arbors. Following injury, shot assists in dendrite regeneration in both neuron types and accumulates in separate shapes in regenerated dendrites, with particular areas crucial for proper Shot accumulation patterns.

These findings establish shot as a context-sensitive regulator of dendrite maintenance and repair, and reveal that the structural identity of a dendritic arbor determines how neurons perceive and respond to cytoskeletal disruptions.