Windpipe Controls Intestinal Homeostasis by Regulating JAK/STAT Pathway via Promoting Receptor Endocytosis and Lysosomal Degradation

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Effective tissue homeostasis requires a proper balance between the removal of dead cells and production of new cells. Due to environmental challenges, the Drosophila midgut epithelial cells are damaged from time to time and intestinal stem cells (ISC) can accelerate their proliferative rate to replace the lost midgut epithelium. The JAK/STAT pathway plays essential roles in these progresses. Upon damage, Upd ligands produced by dying enterocytes (ECs) activate JAK/STAT signaling in ISCs to promote their proliferation and differentiation. However, after damage how JAK/STAT signaling is switched from a highly active state to a homeostatic state is not yet fully understood. In this study, we identified the leucine rich repeats (LRR) protein Windpipe (Wdp) as a novel negative feedback regulator of JAK/STAT signaling during intestinal development. Wdp expression was induced by high levels of JAK/STAT signaling in intestines. And loss of Wdp leads to midgut homeostasis loss and increased ISC proliferation. Furthermore, we found Wdp in turn negatively regulates JAK/STAT signaling activity through promoting Domeless receptor endocytosis and lysosomal degradation. In this way, high levels of JAK/STAT signaling is switched off by Wdp, which ensure ISCs return to the homeostatic state after tissue damage.

Vyšlo v časopise: Windpipe Controls Intestinal Homeostasis by Regulating JAK/STAT Pathway via Promoting Receptor Endocytosis and Lysosomal Degradation. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005180
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005180

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