p38α MAPK is a MTOC-associated protein regulating spindle assembly, spindle length and accurate chromosome segregation during mouse oocyte meiotic maturation.
P38αMAPK (p38α) is usually activated in response to various stresses and plays a role in the inhibition of cell proliferation and tumor progression, but little is known about its roles in meiotic spindle assembly. In this study, we characterized the dynamic localization of p38α and explored its function in mouse oocyte meiotic maturation. P38α specifically colocalized with γ-tubulin and Plk1 at the center of MTOCs and spindle poles. Depletion of p38α by specific morpholino injection resulted in severely defective spindles and misaligned chromosomes probably via MK2 dephosphorylation. Notably, depletion of p38α led to significant spindle pole defects, spindle elongation, non-tethered kinetochore microtubules and increased microtubule tension. The disruption of spindle stability was coupled with decreased γ-tubulin and Plk1 at MTOCs. Overexpression of Eg5, a conserved motor protein, also caused spindle elongation and its morpholino injection almost completely rescued spindle elongation caused by p38α depletion. In addition, p38α-depletion decreased BubR1 and interfered with spindle assembly checkpoint (SAC), which resulted in aneuploid oocytes. Together, these data indicate that p38α is an important component of MTOCs, which regulates spindle assembly and spindle length, as well as stabilizes the spindle and spindle poles. Perturbed SAC and abnormal microtubule tension may be responsible for the misaligned chromosomes and high aneuploidy in p38α-depleted mouse oocytes.
Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Xiang-Hong
XH
Ou
Sen
S
Li
Bao-Zeng
BZ
Xu
Zhen-Bo
ZB
Wang
Song
S
Quan
Mo
M
Li
Qing-Hua
QH
Zhang
Ying-Chun
YC
Ouyang
Heide
H
Schatten
Fu-Qi
FQ
Xing
Qing-Yuan
QY
Sun
D000782:Aneuploidy; D000818:Animals; D020090:Chromosome Segregation; D020868:Gene Silencing; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014404:Tubulin / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins; D048308:Mitogen-Activated Protein Kinase 14; D017346:Protein Serine-Threonine Kinases; D014404:Tubulin; D000099190:MAP-Kinase-Activated Kinase 2; C470243:KIF11 protein, human