Abstract
Sexually reproducing eukaryotes employ a developmentally regulated cell division program-meiosis-to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FoF1-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4ALDH2, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4ALDH2 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 1764-1782.e8 |
| Fachzeitschrift | Developmental Cell |
| Jahrgang | 59 |
| Ausgabenummer | 13 |
| Frühes Online-Datum | 18 Juni 2024 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 8 Juli 2024 |
Fördermittel
We thank Marco Hein for comments on the manuscript. ScopeM at ETH Z\u00FCrich provided instrument access and support for cryo-ET imaging. The Max Perutz Labs BioOptics Light Microscopy facility provided support for the light microscopy experiments. The Beltrao lab is supported by the Helmut Horten Stiftung and the ETH Zurich Foundation. The Pilhofer Lab was supported by the NOMIS Foundation. The Matos Lab was supported by the Swiss National Science Foundation (SNSF) (155823 and 176108), the Austrian Science Foundation FWF (SFB Meiosis\u20148807-B), and the European Research Council (101002629). R.W. performed meiotic time courses for MS experiments with help from M.A.; R.W. and L.G. processed samples for MS; L.G. performed the MS experiments, MS data processing, and initial data analysis; R.W. performed follow-up data analyses; Y.H.-A. performed protein complex, GO, and kinase activity analyses; R.W. performed sporulation efficiency, viability, and spot assays; J.H. performed cryoET experiments and data analysis, with help from F.W.; J.X. generated the structural model of Ald4 filaments; A.H. performed in situ IF experiments; J.v.G. performed kinase phosphorylation motif analyses; J.M. M.P. P.B. and R.A. conceived the study and acquired funding; R.W. and J.M. wrote the initial draft of the manuscript with contributions from M.P. J.H. and P.B.; all authors contributed to the final manuscript. The authors declare no competing interests. We thank Marco Hein for comments on the manuscript. ScopeM at ETH Z\u00FCrich provided instrument access and support for cryo-ET imaging. The Max Perutz Labs BioOptics Light Microscopy facility provided support for the light microscopy experiments. The Beltrao lab is supported by the Helmut Horten Stiftung and the ETH Zurich Foundation . The Pilhofer Lab was supported by the NOMIS Foundation . The Matos Lab was supported by the Swiss National Science Foundation (SNSF) ( 155823 and 176108 ), the Austrian Science Foundation FWF (SFB Meiosis\u2014 8807-B ), and the European Research Council ( 101002629 ).
ÖFOS 2012
- 106023 Molekularbiologie