title: Rab5a is required for spindle length control and kinetochore-microtubule attachment during meiosis in oocytes.
abstract: Rab GTPases are highly conserved components of vesicle trafficking pathways. Rab5, as a master regulator of endocytic trafficking, has been shown to function in membrane tethering and docking. However, the function of Rab5 in meiosis has not been addressed. Here, we report elongated spindles and misaligned chromosomes, with kinetochore-microtubule misattachments, on specific depletion of Rab5a in mouse oocytes. Moreover, the localization and levels of centromere protein F (CENPF), a component of the nuclear matrix, are severely reduced at kinetochores in metaphase oocytes following Rab5a knockdown. Consistent with this finding, nuclear lamina disassembly in the transition from prophase arrest to meiosis I is also impaired in Rab5a-depleted oocytes. Notably, oocyte-specific ablation of CENPF phenocopies the meiotic defects resulting from Rab5a knockdown. In summary, our data support a model where Rab5a-positive vesicles, likely through interaction with nuclear lamina, modulate CENPF localization and levels at centromeres, consequently ensuring proper spindle length and kinetochore-microtubule attachment in meiotic oocytes.
authors.affiliation: College of Veterinary Medicine and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and.
authors.forename: Rujun
authors.initials: R
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Hou
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China;
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Kelle
authors.initials: K
authors.lastname: Moley
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; and qwang2012@njmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D018386:Kinetochores / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology*; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology*; D020696:rab5 GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; D060172:Morpholinos; C094772:centromere protein F; D020696:rab5 GTP-Binding Proteins
keywords: CENPF; chromosome; vesicles