Follicular cells protect Xenopus oocyte from abnormal maturation via integrin signaling downregulation and
Alain Martoriati1, Caroline Molinaro1, Guillaume Marchand1
1University Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
Abstract:
Xenopus oocytes are encompassed by a layer of follicular cells that contribute to oocyte growth and meiosis in relation to oocyte maturation. However, the effects of the interaction between follicular cells and the oocyte surface on meiotic processes are unclear. Here, we investigated Xenopus follicular cell function using oocyte signaling and heterologous-expressing capabilities. We found that oocytes deprotected from their surrounding layer of follicular cells and expressing the epidermal growth factor (EGF) receptor (EGFR) and the Grb7 adaptor undergo accelerated prophase I to metaphase II meiosis progression upon stimulation by EGF. This unusual maturation unravels atypical spindle formation but is rescued by inhibiting integrin β1 or Grb7 binding to the EGFR. In addition, we determined that oocytes surrounded by their follicular cells expressing EGFR-Grb7 exhibit normal meiotic resumption. These oocytes are protected from abnormal meiotic spindle formation through the recruitment of O-GlcNAcylated Grb7, and OGT (O-GlcNAc transferase), the enzyme responsible for O-GlcNAcylation processes, in the integrin β1-EGFR complex. Folliculated oocytes can be forced to adopt an abnormal phenotype and exclusive Grb7 Y338 and Y188 phosphorylation instead of O-GlcNAcylation under integrin activation. Furthermore, an O-GlcNAcylation increase (by inhibition of O-GlcNAcase), the glycosidase that removes O-GlcNAc moieties, or decrease (by inhibition of OGT) amplifies oocyte spindle defects when follicular cells are absent highlighting a control of the meiotic spindle by the OGT-O-GlcNAcase duo. In summary, our study provides further insight into the role of the follicular cell layer in oocyte meiosis progression.
Insights
Xenopus oocytes require follicular cells for normal meiosis. O-GlcNAcylation of Grb7 within the integrin β1-EGFR complex by OGT protects against abnormal spindle formation during oocyte maturation.
Area of Science:
- Cell Biology
- Developmental Biology
- Reproductive Biology
Background:
- Xenopus oocytes are surrounded by follicular cells crucial for growth and maturation.
- The precise role of follicular cell-oocyte interactions in regulating meiosis remains incompletely understood.
Purpose of the Study:
- To investigate the function of Xenopus follicular cells in oocyte meiosis.
- To elucidate the molecular mechanisms underlying the interaction between follicular cells and the oocyte surface during meiotic progression.
Main Methods:
- Utilized Xenopus oocytes with and without follicular cell layers.
- Employed heterologous expression of epidermal growth factor (EGF) receptor (EGFR) and Grb7 adaptor protein.
- Investigated the impact of EGF stimulation, integrin β1 inhibition, and O-GlcNAcylation modulation (using OGT and O-GlcNAcase inhibitors) on meiotic progression and spindle formation.
Main Results:
- Oocytes lacking follicular cells and expressing EGFR-Grb7 showed accelerated meiosis upon EGF stimulation, leading to abnormal spindle formation.
- Inhibition of integrin β1 or Grb7 binding to EGFR rescued abnormal spindle formation in these oocytes.
- Folliculated oocytes expressing EGFR-Grb7 exhibited normal meiotic resumption, protected by O-GlcNAcylated Grb7 recruited to the integrin β1-EGFR complex via OGT.
- Altering O-GlcNAcylation levels (increasing or decreasing) exacerbated spindle defects in de-folliculated oocytes.
Conclusions:
- The follicular cell layer plays a critical role in maintaining meiotic fidelity during Xenopus oocyte maturation.
- O-GlcNAcylation, mediated by OGT and regulated by O-GlcNAcase, is essential for preventing abnormal meiotic spindle formation, particularly in the context of the integrin β1-EGFR complex.
- Follicular cell-oocyte interactions, involving EGFR, Grb7, and O-GlcNAcylation, are vital for normal oocyte meiotic progression.
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