Translatome analysis reveals cellular network in DLK-dependent hippocampal glutamatergic neuron degeneration

Published: Sept. 10, 2024

The conserved MAP3K12/Dual Leucine Zipper Kinase (DLK) plays versatile roles in neuronal development, axon injury and stress responses, neurodegeneration, depending on cell-type cellular contexts. Emerging evidence implicates abnormal DLK signaling several neurodegenerative diseases. However, our understanding of the DLK-dependent gene network central nervous system remains limited. Here, we investigated hippocampal glutamatergic neurons using conditional knockout induced overexpression mice. We found that dorsal CA1 dentate gyrus are vulnerable to elevated expression DLK, while CA3 appear largely unaffected. identified translatome includes molecular signatures displays specificity. Increasing is associated with disruptions microtubules, potentially involving STMN4. Additionally, primary cultured expressing different levels show altered neurite outgrowth, specification, synapse formation. identification translational targets has relevance

Language: Английский

Axonal injury signaling is restrained by a spared synaptic branch

Published: Dec. 27, 2024

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

Language: Английский

Axonal injury signaling is restrained by a spared synaptic branch

Published: Dec. 27, 2024

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

Language: Английский