MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment.
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.
Yuan
Ju
J
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Xu
Bao-Zeng
BZ
Qi
Shu-Tao
ST
Tong
Jing-Shan
JS
Wei
Liang
L
Li
Mo
M
Ouyang
Ying-Chun
YC
Hou
Yi
Y
Schatten
Heide
H
Sun
Qing-Yuan
QY
D000818:Animals; D018386:Kinetochores / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D008540:Meiosis; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D008941:Spindle Apparatus; D013347:Subcellular Fractions / Q000201:enzymology
D048370:MAP Kinase Kinase 2; D017239:Paclitaxel; D015739:Nocodazole