Journal Article

Axonal injury signaling is restrained by a spared synaptic branch

Junginger, Lucas, Li, Ye, Waller, Thomas J, Reilly-Jankowiak, Lauren, Collins, Catherine A, Smithson, Laura J, Zang, Juliana L, Khan, Sophia A, Cai, Dawen

2025

Overview

The intrinsic ability of injured neurons to degenerate and regenerate their axons facilitates nervous system repair; however, this ability is not engaged in all neurons and injury locations. Here, we investigate the regulation of a conserved axonal injury response pathway with respect to the location of damage in branched motoneuron (MN) axons in Drosophila larvae. The dileucine zipper kinase (DLK; also known as MAP3K12 in mammals and Wallenda (Wnd) in Drosophila ) is a key regulator of diverse responses to axonal injury. In three different populations of MNs, we observed the same striking result that Wnd/DLK signaling becomes activated only in response to injuries that remove all synaptic terminals. Injuries that spared even a small part of a synaptic terminal were insufficient to activate Wnd/DLK signaling, despite the presence of extensive axonal degeneration. The regulation of injury-induced Wnd/DLK signaling occurs independently of its previously known regulator, the Hiw/PHR ubiquitin ligase. We propose that Wnd/DLK signaling regulation is linked to the trafficking of a synapse-to-nucleus axonal cargo and that this mechanism enables neurons to respond to impairments in synaptic connectivity.

• Publisher: eLife Sciences Publications Ltd
• Subject: Animals / axonal degeneration / axonal injury signaling / axonal regeneration / Axons - metabolism / Axons - pathology / Axons - physiology / Drosophila / Drosophila melanogaster / Drosophila Proteins - metabolism / Larva / MAP Kinase Kinase Kinases - metabolism / Motor Neurons - metabolism / Motor Neurons - physiology / Nerve Tissue Proteins / Signal Transduction / spared synapse / structural plasticity / Synapses - metabolism