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The GTPase SPAG-1 orchestrates meiotic program by dictating meiotic resumption and cytoskeleton architecture in mouse oocytes.

Mol. Biol. Cell. 2016 Jun 01;27(11):1776-85. Epub 2016 Apr 06
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摘要


In mammals, a finite population of oocytes is generated during embryogenesis, and proper oocyte meiotic divisions are crucial for fertility. Sperm-associated antigen 1 has been implicated in infertility and tumorigenesis; however, its relevance in cell cycle programs remains rudimentary. Here we explore a novel role of during oocyte meiotic progression. duanyu1842G-1 associated with meiotic spindles and its depletion severely compromised M-phase entry (germinal vesicle breakdown [GVBD]) and polar body extrusion. The GVBD defect observed was due to an increase in intraoocyte cAMP abundance and decrease in ATP production, as confirmed by the activation of AMP-dependent kinase (AMPK). duanyu1842G-1 RNA interference defective spindle morphogenesis was evidenced by the dysfunction of γ-tubulin, which resulted from substantially reduced phosphorylation of MAPK and irregularly dispersed distribution of phospho-MAPK around spindles instead of concentration at spindle poles. Significantly, actin expression abruptly decreased and formation of cortical granule-free domains, actin caps, and contractile ring disrupted by duanyu1842G-1 In addition, the spindle assembly checkpoint remained functional upon duanyu1842G-1 depletion. The findings broaden our knowledge of showing that it exerts a role in oocyte meiotic execution via its involvement in AMPK and MAPK signaling pathways.

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