Abstract

Epsins are a conserved family of endocytic adaptors essential for diverse biological events. However, its role in oocytes remains completely unknown. Here, we report that specific depletion of Epsin2 in mouse oocytes significantly disrupts meiotic progression. Confocal microscopy reveals that Epsin2 knockdown results in the failure of actin cap formation and polar body extrusion during meiosis, indicative of the importance of Epsin2 in polarity establishment and cytokinesis. In addition, spindle defects and chromosome misalignment are readily observed in oocytes depleted of Epsin2. Moreover, we find that Epsin2 knockdown markedly decreases the activity of Cdc42 in oocytes and importantly, that the dominant-positive mutant of Cdc42 (Cdc42Q61L) is capable of partially rescuing the deficient phenotypes of Epsin2-knockdown oocytes. Together, our data identify Epsin2 as a novel player in regulating oocyte maturation, and demonstrate that Epsin2 promotes polarity establishment and meiotic division via activating Cdc42.

Highlights

  • In both vertebrates and invertebrates, oocyte meiotic maturation is to generate a haploid gamete through two consecutive divisions, resulting in formation of a large oocyte and two small polar bodies [1]

  • By employing knockdown and overexpression analysis, we found that Epsin2 is predominately expressed in mouse oocyte, and specific depletion of Epsin2 disrupts the formation of actin cap and prevents polar body emission through affecting Cdc42 activity

  • We first evaluated the expression of different isoforms of Epsins in both germinal vesicle (GV) and metaphase II (MII)-stage oocytes

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Summary

Introduction

In both vertebrates and invertebrates, oocyte meiotic maturation is to generate a haploid gamete through two consecutive divisions, resulting in formation of a large oocyte and two small polar bodies [1]. By position the spindle from oocyte center to the cortex in meiosis I (MI), oocyte symmetry is broken and cortical polarity is established [2]. Cortex-located chromosomes induce a series of cortical remolding in oocytes, including disappearance of membrane microvilli, formation of a thick F-actin cap, and polarized accumulation of related molecules [3, 4]. This specialized cortical region defines the site of cytokinesis and polar body extrusion. Cdc was identified as a critical molecular cascade initiated by Ran to establish polarity and control cytokinesis of oocytes [3, 6, 7]

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