title: The role of RanGTP gradient in vertebrate oocyte maturation.
abstract: The maturation of vertebrate oocyte into haploid gamete, the egg, consists of two specialized asymmetric cell divisions with no intervening S-phase. Ran GTPase has an essential role in relaying the active role of chromosomes in their own segregation by the meiotic process. In addition to its conserved role as a key regulator of macromolecular transport between nucleus and cytoplasm, Ran has important functions during cell division, including in mitotic spindle assembly and in the assembly of nuclear envelope at the exit from mitosis. The cellular functions of Ran are mediated by RanGTP interactions with nuclear transport receptors (NTRs) related to importin β and depend on the existence of chromosome-centered RanGTP gradient. Live imaging with FRET biosensors indeed revealed the existence of RanGTP gradient throughout mouse oocyte maturation. NTR-dependent transport of cell cycle regulators including cyclin B1, Wee2, and Cdc25B between the oocyte cytoplasm and germinal vesicle (GV) is required for normal resumption of meiosis. After GVBD in mouse oocytes, RanGTP gradient is required for timely meiosis I (MI) spindle assembly and provides long-range signal directing egg cortex differentiation. However, RanGTP gradient is not required for MI spindle migration and may be dispensable for MI spindle function in chromosome segregation. In contrast, MII spindle assembly and function in maturing mouse and Xenopus laevis eggs depend on RanGTP gradient, similar to X. laevis MII-derived egg extracts.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892-4256, USA. kalab@mail.nih.gov
authors.forename: Petr
authors.initials: P
authors.lastname: Kaláb
authors.forename: Petr
authors.initials: P
authors.lastname: Solc
authors.forename: Jan
authors.initials: J
authors.lastname: Motlík
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology*; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000502:physiology; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein