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Proteasome α6 Subunit Negatively Regulates the JAK/STAT Pathway and Blood Cell Activation in Drosophila melanogaster

Mirva Järvelä-Stölting1, Laura Vesala1, Matthew K Maasdorp1

  • 1Laboratory of Experimental Immunology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Frontiers in Immunology
|January 10, 2022
PubMed

Insights

The proteasome complex, including Prosα6, negatively regulates Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling in Drosophila blood cells. Its inhibition activates this pathway, leading to immune cell activation.

Area of Science:

  • * Molecular Biology
  • * Cell Biology
  • * Immunology

Background:

  • * The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is crucial for development, cell differentiation, and immune responses.
  • * Misregulated JAK/STAT signaling in Drosophila hemocytes leads to their abnormal activation.

Purpose of the Study:

  • * To identify novel negative regulators of JAK/STAT signaling in Drosophila hemocytes.
  • * To investigate the role of proteasome complex components in regulating JAK/STAT signaling.

Main Methods:

  • * Mass spectrometry was used to analyze proteins associated with a known negative regulator of the JAK/STAT pathway.
  • * A genome-wide RNAi screen was performed to identify regulatory components.
  • * The function of a specific proteasome component, Prosα6, was studied in S2 cells and in vivo.

Main Results:

  • * Several proteasome complex components were identified as negative regulators of JAK/STAT signaling.
  • * Silencing of Prosα6 in S2 cells reduced the levels of the negative regulator ET, enhancing reporter gene expression.
  • * In vivo silencing of Prosα6 activated the JAK/STAT pathway, inducing lamellocyte formation, a marker of hemocyte activation.
  • * This phenotype was partially rescued by knocking down the Drosophila STAT or MAPKK.

Conclusions:

  • * Proteasome complex components play a role in regulating JAK/STAT signaling in Drosophila blood cells.
  • * Prosα6 acts as a negative regulator, and its inhibition leads to hemocyte activation.
  • * These findings highlight a novel link between proteasome function and immune regulation in Drosophila.

Keywords:
Drosophila melanogasterEye TransformerJAK/STAT pathwayRNA interferencefruit flyhemocytelamellocytethe proteasome complex

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