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Tousled-like kinase mediated a new type of cell death pathway in Drosophila

Y Zhang1,2, R Cai1,2, R Zhou2

  • 1State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.

Cell Death and Differentiation
|June 20, 2015
PubMed

Insights

Tousled-like kinase (TLK) triggers a novel cell death pathway in Drosophila, independent of known mechanisms. ATG2 acts downstream of TLK, influencing both developmental and calcium-induced cell death.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Programmed cell death (PCD) is crucial for organism development.
  • The molecular mechanisms underlying PCD are not fully understood.
  • Canonical caspase pathways and known caspase-independent pathways do not fully explain all forms of PCD.

Purpose of the Study:

  • To investigate a novel type of cell death induced by ectopic expression of tousled-like kinase (TLK) in Drosophila.
  • To elucidate the molecular mechanism of TLK-induced cell death and its relationship with ATG2.
  • To determine the role of TLK and ATG2 in developmental PCD and calcium cytotoxicity.

Main Methods:

  • Ectopic expression of tousled-like kinase (TLK) in Drosophila.
  • RNA interference (RNAi) to knockdown atg2.
  • Analysis of cell death in developing retina, specifically interommatidial cells (IOCs).
  • Assessment of TLK and ATG2 roles in calcium overload-induced cell death.

Main Results:

  • Ectopic TLK expression induced a novel form of cell death in Drosophila.
  • TLK-induced cell death was independent of canonical caspase pathways and other known caspase-independent pathways.
  • ATG2 knockdown rescued TLK-induced cell death, suggesting ATG2 functions downstream of TLK.
  • Loss of TLK reduced PCD in developing retinal IOCs, while ATG2 deletion increased IOCs.
  • TLK and ATG2 RNAi could rescue calcium overload-induced cell death.

Conclusions:

  • TLK mediates a novel cell death pathway in Drosophila.
  • This pathway is distinct from known caspase-dependent and independent cell death mechanisms.
  • ATG2 plays a role downstream of TLK in both developmental PCD and calcium cytotoxicity.

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