TY - JOUR
T1 - The response of Dual-leucine zipper kinase (DLK) to nocodazole
T2 - Evidence for a homeostatic cytoskeletal repair mechanism
AU - DeVault, Laura
AU - Mateusiak, Chase
AU - Palucki, John
AU - Brent, Michael
AU - Milbrandt, Jeffrey
AU - DiAntonio, Aaron
N1 - Publisher Copyright:
© 2024 Public Library of Science. All rights reserved.
PY - 2024/4
Y1 - 2024/4
N2 - Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNAseq. This signature includes genes likely to attenuate DLK signaling while simultaneously inducing actin regulating genes. We identify alterations to the cytoskeleton including actinbased morphological changes to the axon. These results are consistent with the model that cytoskeletal disruption in the neuron induces a DLK-dependent homeostatic mechanism, which we term the Cytoskeletal Stress Response (CSR) pathway.
AB - Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNAseq. This signature includes genes likely to attenuate DLK signaling while simultaneously inducing actin regulating genes. We identify alterations to the cytoskeleton including actinbased morphological changes to the axon. These results are consistent with the model that cytoskeletal disruption in the neuron induces a DLK-dependent homeostatic mechanism, which we term the Cytoskeletal Stress Response (CSR) pathway.
UR - http://www.scopus.com/inward/record.url?scp=85189312030&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0300539
DO - 10.1371/journal.pone.0300539
M3 - Article
C2 - 38574058
AN - SCOPUS:85189312030
SN - 1932-6203
VL - 19
JO - PloS one
JF - PloS one
IS - 4 April
M1 - e0300539
ER -