RRC ID 73801
Author Liu S, Baeg GH, Yang Y, Goh FG, Bao H, Wagner EJ, Yang X, Cai Y.
Title The Integrator complex desensitizes cellular response to TGF-β/BMP signaling.
Journal Cell Rep
Abstract Maintenance of stem cells requires the concerted actions of niche-derived signals and stem cell-intrinsic factors. Although Decapentaplegic (Dpp), a Drosophila bone morphogenetic protein (BMP) molecule, can act as a long-range morphogen, its function is spatially limited to the germline stem cell niche in the germarium. We show here that Integrator, a complex known to be involved in RNA polymerase II (RNAPII)-mediated transcriptional regulation in the nucleus, promotes germline differentiation by restricting niche-derived Dpp/BMP activity in the cytoplasm. Further results show that Integrator works in various developmental contexts to desensitize the cellular response to Dpp/BMP signaling during Drosophila development. Mechanistically, our results show that Integrator forms a multi-subunit complex with the type I receptor Thickveins (Tkv) and other Dpp/BMP signaling components and acts in a negative feedback loop to promote Tkv turnover independent of its transcriptional activity. Similarly, human Integrator subunits bind transforming growth factor β (TGF-β)/BMP signaling components and antagonize their activity, suggesting a conserved role of Integrator across metazoans.
Volume 42(1)
Pages 112007
Published 2023-1-31
DOI 10.1016/j.celrep.2023.112007
PII S2211-1247(23)00018-9
PMID 36641752
MeSH Animals Bone Morphogenetic Proteins / metabolism Cell Differentiation / physiology Drosophila / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Humans Protein Serine-Threonine Kinases / metabolism Receptors, Cell Surface / metabolism Signal Transduction / physiology Transforming Growth Factor beta* / metabolism
IF 8.109