Two PAR6 Proteins Become Asymmetrically Localized during Establishment of Polarity in Mouse Oocytes

Abstract

Meiotic maturation in mammals is characterized by two asymmetric divisions, leading to the formation of two polar bodies and the female gamete. Whereas the mouse oocyte is a polarized cell, molecules implicated in the establishment of this polarity are still unknown. PAR proteins have been demonstrated to play an important role in cell polarity in many cell types, where they control spindle positioning and asymmetric distribution of determinants. Here we show that two PAR6-related proteins have distinct polarized distributions in mouse oocytes. mPARD6a is first localized on the spindle and then accumulates at the pole nearest the cortex during spindle migration. In the absence of microtubules, the chromosomes still migrate to the cortex, and mPARD6a was found associated with the chromosomes and was facing the cortex. mPARD6a is the first identified protein to associate with the spindle during spindle migration and to relocalize to the chromosomes in the absence of microtubule behavior, suggesting a role in spindle migration. The other protein, mPARD6b, was found on spindle microtubules until entry into meiosis II and relocalized to the cortex at the animal pole during metaphase II arrest. mPARD6b is the first identified protein to localize to the animal pole of the mouse oocyte and likely contributes to the polarization of the cortex.

Actin cytoskeleton in cell polarity and asymmetric division during mouse oocyte maturation

“…The Par proteins have been demonstrated to be crucial for polarity establishment in many cell types [Cowan and Hyman, 2004;Goldstein and Macara, 2007]. In mouse oocytes, PAR1, PAR4, and aPKC are localized to meiotic spindles [Baluch et al, 2004;Vinot et al, 2004;Duncan et al, 2005;Moore and Zernicka-Goetz, 2005;Szczepanska and Maleszewski, 2005;Na and Zernicka-Goetz, 2006]. aPKC accumulates at spindle poles and may play a role in regulating spindle MTs, as disruption of this distribution by Cdc42 perturbation results in abnormal spindle morphology [Na and Zernicka-Goetz, 2006].…”

“…aPKC accumulates at spindle poles and may play a role in regulating spindle MTs, as disruption of this distribution by Cdc42 perturbation results in abnormal spindle morphology [Na and Zernicka-Goetz, 2006]. Two Par proteins, PAR3 and PAR6b, are first associated with the meiotic spindle and later relocalized to the MI and MII cortical cap [Vinot et al, 2004;Duncan et al, 2005]. Further functional data on how the Par proteins might be involved in oocyte polarity and asymmetric division are still lacking.…”

Polar body cytokinesis

“…In mouse oocytes, PAR-3 is associated with the cortex adjacent to the meiotic spindle [Duncan et al, 2005] in a manner dependent on the cortical differentiated zone [Luo et al 2009]. One isoform of PAR-6, mPAR6b also accumulates at the cortical differentiated area during metaphase II arrest in mouse [Vinot et al, 2004]. However, any functional link between PAR proteins and Cdc42, as well as PAR proteins' function in PBE, remains to be established.…”

Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space

“…During MI, PARD6A is concentrated on the spindle half that leads the migration. Upon microtubule depolymerization it concentrates on the surface of the chromosomes oriented toward the cortex (Vinot et al 2004). It may be part of a multi-protein complex coupling chromosomes, microtubules and actin microfilaments and support spindle motility and anchoring.…”