RRC ID 58325
Author Rastegari E, Kajal K, Tan BS, Huang F, Chen RH, Hsieh TS, Hsu HJ.
Title WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.
Journal Development
Abstract WD40 proteins control many cellular processes via protein interactions. Drosophila Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Wh and Mei-p26 are epistatically linked, with wh and mei-p26 mutants showing nearly identical phenotypes, including germline stem cell (GSC) loss, stem-cyst formation due to incomplete cytokinesis between GSCs and daughter cells, and overproliferation of GSC progeny. Mechanistically, Wh interacts with Mei-p26 in different cellular contexts to induce cell type-specific effects. In GSCs, Wh and Mei-p26 promote BMP stemness signaling for proper GSC division and maintenance. In GSC progeny, Wh and Mei-p26 silence nanos translation, downregulate a subset of microRNAs involved in germ cell differentiation and suppress ribosomal biogenesis via dMyc to limit germ cell mitosis. We also found that the human ortholog of Wh (WDR4) interacts with TRIM32 in human cells. Our results show that Wh is a regulator of Mei-p26 in Drosophila germ cells and suggest that the WD40-TRIM interaction may also control tissue homeostasis in other stem cell systems.
Volume 147(2)
Published 2020-1-15
DOI 10.1242/dev.182063
PII 147/2/dev182063
PMID 31941704
PMC PMC7375833
MeSH Animals Bone Morphogenetic Proteins / metabolism Carrier Proteins / metabolism* Cell Differentiation Conserved Sequence Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / metabolism* Evolution, Molecular Female Fertility Germ Cells / cytology Germ Cells / metabolism* Homeostasis* Meiosis MicroRNAs / genetics MicroRNAs / metabolism Mitosis Models, Biological Mutation / genetics Ovary / cytology Ovum / cytology Ovum / metabolism Phenotype Protein Binding Ribosomes / metabolism Signal Transduction
IF 5.611
Times Cited 0