Proteasome α6 subunit negatively regulates the JAK/STAT pathway and blood cell activation in <em>Drosophila melanogaster</em>
Järvelä-Stölting, Mirva; Vesala, Laura; Maasdorp, Matthew K.; Ciantar, Joanna; Rämet, Mika; Valanne, Susanna (2021-12-22)
Järvelä-Stölting M, Vesala L, Maasdorp MK, Ciantar J, Rämet M and Valanne S (2021) Proteasome α6 Subunit Negatively Regulates the JAK/STAT Pathway and Blood Cell Activation in Drosophila melanogaster. Front. Immunol. 12:729631. doi: 10.3389/fimmu.2021.729631
© 2021 Järvelä-Stölting, Vesala, Maasdorp, Ciantar, Rämet and Valanne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2022022220342
Tiivistelmä
Abstract
JAK/STAT signaling regulates central biological functions such as development, cell differentiation and immune responses. In Drosophila, misregulated JAK/STAT signaling in blood cells (hemocytes) induces their aberrant activation. Using mass spectrometry to analyze proteins associated with a negative regulator of the JAK/STAT pathway, and by performing a genome-wide RNAi screen, we identified several components of the proteasome complex as negative regulators of JAK/STAT signaling in Drosophila. A selected proteasome component, Prosα6, was studied further. In S2 cells, Prosα6 silencing decreased the amount of the known negative regulator of the pathway, ET, leading to enhanced expression of a JAK/STAT pathway reporter gene. Silencing of Prosα6 in vivo resulted in activation of the JAK/STAT pathway, leading to the formation of lamellocytes, a specific hemocyte type indicative of hemocyte activation. This hemocyte phenotype could be partially rescued by simultaneous knockdown of either the Drosophila STAT transcription factor, or MAPKK in the JNK-pathway. Our results suggest a role for the proteasome complex components in the JAK/STAT pathway in Drosophila blood cells both in vitro and in vivo.
Kokoelmat
- Avoin saatavuus [31995]