Systematic analysis of F-box proteins reveals a new branch of the yeast mating pathway.
Nambirajan RangarajanClaire L GordyLauren AskewSamantha M BevillTimothy C ElstonBeverly ErredeJillian H HurstJoshua B KelleyJoshua B SheetzSara Kimiko SuzukiNatalie H ValentinEverett YoungHenrik G DohlmanPublished in: The Journal of biological chemistry (2019)
The mating pathway in yeast Saccharomyces cerevisiae has long been used to reveal new mechanisms of signal transduction. The pathway comprises a pheromone receptor, a heterotrimeric G protein, and intracellular effectors of morphogenesis and transcription. Polarized cell growth, in the direction of a potential mating partner, is accomplished by the G-protein βγ subunits and the small G-protein Cdc42. Transcription induction, needed for cell-cell fusion, is mediated by Gβγ and the mitogen-activated protein kinase (MAPK) scaffold protein Ste5. A potential third pathway is initiated by the G-protein α subunit Gpa1. Gpa1 signaling was shown previously to involve the F-box adaptor protein Dia2 and an endosomal effector protein, the phosphatidylinositol 3-kinase Vps34. Vps34 is also required for proper vacuolar sorting and autophagy. Here, using a panel of reporter assays, we demonstrate that mating pheromone stimulates vacuolar targeting of a cytoplasmic reporter protein and that this process depends on Vps34. Through a systematic analysis of F-box deletion mutants, we show that Dia2 is required to sustain pheromone-induced vacuolar targeting. We also found that other F-box proteins selectively regulate morphogenesis (Ydr306, renamed Pfu1) and transcription (Ucc1). These findings point to the existence of a new and distinct branch of the pheromone-signaling pathway, one that likely leads to vacuolar engulfment of cytoplasmic proteins and recycling of cellular contents in preparation for mating.
Keyphrases
- binding protein
- transcription factor
- saccharomyces cerevisiae
- signaling pathway
- single cell
- protein protein
- protein kinase
- amino acid
- pi k akt
- cell therapy
- stem cells
- immune response
- small molecule
- crispr cas
- mass spectrometry
- dna methylation
- bone marrow
- hepatitis c virus
- mesenchymal stem cells
- regulatory t cells
- cell cycle
- induced apoptosis
- high resolution
- reactive oxygen species
- drug delivery
- cell proliferation
- hiv infected
- endothelial cells
- molecularly imprinted
- type iii