TY - JOUR
T1 - Kif4 is essential for mouse oocyte meiosis
AU - Camlin, Nicole J.
AU - McLaughlin, Eileen A.
AU - Holt, Janet E.
N1 - Publisher Copyright:
© 2017 Camlin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENPC. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.
AB - Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENPC. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.
KW - Oocytes
KW - Meiosis
KW - assembly checkpoint
KW - Kinetochores/metabolism
KW - Meiosis/genetics
KW - Aurora Kinase B/genetics
KW - Phosphorylation
KW - Chromosomal Proteins, Non-Histone/genetics
KW - Polar Bodies
KW - Microtubule-Associated Proteins/genetics
KW - Animals
KW - Oocytes/growth & development
KW - Gene Expression Regulation, Developmental/genetics
KW - Microtubules/genetics
KW - Cell Cycle Proteins/genetics
KW - Mice
KW - Mitosis/genetics
KW - Kinesin/genetics
KW - CDC2 Protein Kinase/genetics
UR - http://www.scopus.com/inward/record.url?scp=85010898401&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/kif4-essential-mouse-oocyte-meiosis
U2 - 10.1371/journal.pone.0170650
DO - 10.1371/journal.pone.0170650
M3 - Article
C2 - 28125646
AN - SCOPUS:85010898401
SN - 1932-6203
VL - 12
SP - 1
EP - 10
JO - PLoS One
JF - PLoS One
IS - 1
M1 - e0170650
ER -