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Label-Free Non-Linear Optics for the Study of Tubulin-Dependent Defects in Central Myelin
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Microtubule disruption upon CNS damage triggers mitotic entry via TNF signaling activation

Claudia S Barros1, Torsten Bossing1

  • 1Peninsula Medical School, Faculty of Health, University of Plymouth, John Bull Building, 16 Research Way, Plymouth PL6 8BU, UK.

Cell Reports
|July 7, 2021
PubMed

Insights

Traumatic injury triggers cell division via microtubule disruption and TNF signaling. This pathway, involving Tak1 and Ik2, is conserved in Alzheimer

Area of Science:

  • Neurobiology
  • Cellular Biology
  • Developmental Biology

Background:

  • Cellular repair after injury often involves cell division.
  • Microtubule disruption is implicated in traumatic injury and neurodegenerative diseases like Alzheimer's disease (AD).

Purpose of the Study:

  • To investigate the molecular mechanisms linking microtubule disruption to cell division.
  • To explore the role of tumor necrosis factor (TNF) signaling in response to cellular damage.
  • To determine if the observed mechanisms are relevant to Alzheimer's disease.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism.
  • Induced microtubule disruption in embryonic central nervous system (CNS) midline cells.
  • Expressed human Tau protein in Drosophila midline cells.
  • Analyzed protein phosphorylation, nuclear translocation, and gene expression.
  • Examined protein activation in human Alzheimer's disease brain samples.

Main Results:

  • Microtubule disruption activates non-canonical TNF signaling through TGF-β activated kinase 1 (Tak1) and IkappaB kinase (Ik2).
  • This signaling cascade leads to Dorsal/NfkappaB nuclear translocation and Jra/Jun expression, promoting cell division.
  • Tak1 and Ik2 are essential for damage-induced cell divisions.
  • Expression of human Tau in Drosophila recapitulates these molecular events and induces cell division.
  • Activation of Tak1, its human ortholog Tank binding kinase 1 (Tbk1), and NfkappaB is observed in AD brains.

Conclusions:

  • Microtubule disruption is a potent activator of cell division via non-canonical TNF signaling.
  • The identified pathway involving Tak1 and Ik2 is crucial for cellular repair following injury.
  • The conserved mechanism highlights a potential link between Tau pathology, microtubule disruption, and cellular responses in Alzheimer's disease.
Keywords:
Alzheimer's diseaseDrosophilaTak1Tbk1microtubulesmitosisneuronal damagetissue damageventral midline

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