TY - JOUR
T1 - Chromokinesin Kif4 promotes proper anaphase in mouse oocyte meiosis
AU - Heath, Carissa M.
AU - Wignall, Sarah M.
N1 - Funding Information:
Fixed immunofluorescence images were acquired on a DeltaVision Core deconvolution microscope with a 100× objective (NA = 1.4; Applied Precision). The DeltaVision microscope is housed by North-western’s Biological Imaging Facility supported by the Northwestern University Office for Research. Image stacks were taken with a 0.2-µm step size and deconvolved using SoftWoRx (Applied Precision). The images in this study were deconvolved (unless otherwise noted) and represent maximum projections of full or partial spindles as noted in the figures and legends.
Funding Information:
We thank Teresa Woodruff, members of the Wignall and Woodruff labs, and the WiLa Cell Biology Group for their help and support; Amanda Davis-Roca, Nikita Divekar, Jeremy Hollis, Rachel Kadzik, Tim Mullen, and Ian Wolff for critical reading of the manuscript; and Joseph Draut for initial anaphase spindle characterization work. This work was supported by a March of Dimes Research Grant and by National Institutes of Health R01GM124354 (to S.M.W.) and by the Cell and Molecular Basis of Disease Training Program at Northwestern University, Grant no. T32GM008061 (to C.M.H.).
Publisher Copyright:
© 2019 Heath and Wignall.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Oocytes of many species lack centrioles and therefore form acentriolar spindles. Despite the necessity of oocyte meiosis for successful reproduction, how these spindles mediate accurate chromosome segregation is poorly understood. We have gained insight into this process through studies of the kinesin-4 family member Kif4 in mouse oocytes. We found that Kif4 localizes to chromosomes through metaphase and then largely redistributes to the spindle midzone during anaphase, transitioning from stretches along microtubules to distinct ring-like structures; these structures then appear to fuse together by telophase. Kif4's binding partner PRC1 and MgcRacGAP, a component of the centralspindlin complex, have a similar localization pattern, demonstrating dynamic spindle midzone organization in oocytes. Kif4 knockdown results in defective midzone formation and longer spindles, revealing new anaphase roles for Kif4 in mouse oocytes. Moreover, inhibition of Aurora B/C kinases results in Kif4 mislocalization and causes anaphase defects. Taken together, our work reveals essential roles for Kif4 during the meiotic divisions, furthering our understanding of mechanisms promoting accurate chromosome segregation in acentriolar oocytes.
AB - Oocytes of many species lack centrioles and therefore form acentriolar spindles. Despite the necessity of oocyte meiosis for successful reproduction, how these spindles mediate accurate chromosome segregation is poorly understood. We have gained insight into this process through studies of the kinesin-4 family member Kif4 in mouse oocytes. We found that Kif4 localizes to chromosomes through metaphase and then largely redistributes to the spindle midzone during anaphase, transitioning from stretches along microtubules to distinct ring-like structures; these structures then appear to fuse together by telophase. Kif4's binding partner PRC1 and MgcRacGAP, a component of the centralspindlin complex, have a similar localization pattern, demonstrating dynamic spindle midzone organization in oocytes. Kif4 knockdown results in defective midzone formation and longer spindles, revealing new anaphase roles for Kif4 in mouse oocytes. Moreover, inhibition of Aurora B/C kinases results in Kif4 mislocalization and causes anaphase defects. Taken together, our work reveals essential roles for Kif4 during the meiotic divisions, furthering our understanding of mechanisms promoting accurate chromosome segregation in acentriolar oocytes.
UR - http://www.scopus.com/inward/record.url?scp=85069237336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069237336&partnerID=8YFLogxK
U2 - 10.1091/mbc.E18-10-0666
DO - 10.1091/mbc.E18-10-0666
M3 - Article
C2 - 31067151
AN - SCOPUS:85069237336
VL - 30
SP - 1691
EP - 1704
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 14
ER -