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

Authors

Duarte, V. N., Brichko, R., Najafi, V., Thompson-Peer, K. L.

Abstract

Dendrites are vital to neuronal function, and dendrite injury occurs after neurological traumas such as stroke, traumatic brain injury, or neurodegenerative diseases. Despite their importance, the mechanisms underlying dendrite maintenance or regeneration remain poorly understood. The Drosophila gene short stop (shot), orthologous to ACF7/MACF1 in mammals, functions as an actin-microtubule crosslinker during neuronal development. Here, we investigate shot's role in dendrite stability and repair using Drosophila sensory neurons. We find that shot plays opposing, cell type-specific roles in dendrite maintenance: it restricts excessive branch growth in simple, stable neurons, while being required for dendrite coverage in complex, dynamic neurons. These opposing functions are reflected in distinct localization patterns in stable versus dynamic dendrite arbors. Loss of shot destabilizes the microtubule cytoskeleton in stable neurons, and activates Wallenda/DLK signaling in both stable and dynamic neurons. Downstream of Wallenda/DLK, JNK signaling diverges between neuron types, with canonical basket/JNK activation occurring only in neurons with stable dendritic arbors. After injury, shot promotes dendrite regeneration in both neuron types and accumulates in distinct shapes in regenerated dendrites, with specific domains critical for proper Shot accumulation patterns. Collectively, these findings establish shot as a context-dependent regulator of dendrite maintenance and repair, and demonstrate that the structural identity of a dendritic arbor shapes how neurons sense and respond to cytoskeletal perturbation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 09 Sep 2026.

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