Abstract
MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments.
Highlights
A fundamental property of life is the ability to reproduce
To examine the expression level of p-Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in mouse oocytes at different stages of meiotic maturation, samples were collected after oocytes had been cultured for 0, 4, 8, 9.5, and 12 h, corresponding to germinal vesicle (GV), prometaphase I (Pro-MI), metaphase I (MI), telophase I (TI), and metaphase II (MII) stages, respectively
Chromatin interaction with microtubules appears to influence microtubule dynamics, a bipolar spindle can still form in the absence of chromatin, as is the case in enucleated mouse oocytes [45,46]
Summary
A fundamental property of life is the ability to reproduce. Mitosis and meiosis are essential for development and utilized by organisms to pass on their genetic information. Spindle assembly involves coordinated activities of multiple proteins resulting in localized microtubule nucleation, dynamics, and organization, including Plk1 [5], Aurora A [6], and Astrin [7]. The cohesin protein complex is essential for cohesion in both mitosis and meiosis, and cleavage of one of the subunits is sufficient for chromosome segregation at anaphase [11]. Studies in the last decade revealed that MAPK cascade plays pivotal roles in regulating the meiotic cell cycle progression of oocytes [21,22], microtubule organization and spindle assembly during mammalian oocyte meiosis [23,24,25]. We show for the first time that MK2 may regulate bipolar spindle stability, microtubule-kinetochore attachments and chromosome segregation to participate in meiotic cell cycle regulation
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