title: Distribution and association of mTOR with its cofactors, raptor and rictor, in cumulus cells and oocytes during meiotic maturation in mice.
abstract: Mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase, is the catalytic component of two distinct signaling complexes, mTOR-raptor complex (mTORC1) and mTOR-rictor complex (mTORC2). Recently, studies have demonstrated mitosis-specific roles for mTORC1, but the functions and expression dynamics of mTOR complexes during meiotic maturation remain unclear. In the present study, to evaluate the roles of respective mTOR complexes in maternal meiosis and compare them with those in mitosis, we sought to elucidate the spatiotemporal immunolocalization of mTOR, the kinase-active Ser2448- and Ser2481-phosphorylated mTOR, and raptor and rictor during cumulus-cell mitosis and oocyte meiotic maturation in mice. mTOR principally accumulated around the chromosomes and on the spindle. Phosphorylated mTOR (Ser2448 and Ser2481) exhibited elevated fluorescence intensities in the cytoplasm and punctate localization adjacent to the chromosomes, on the spindle poles, and on the midbody during mitotic and meiotic maturation, suggesting functional homology of mTOR between the two cell division systems, despite their mechanistically distinctive spindles. Raptor colocalized with mTOR during both types of cell division, indicating that mTORC1 is predominantly associated with these events. Mitotic rictor uniformly distributed through the cytoplasm, and meiotic rictor localized around the spindle poles of metaphase-I oocytes, suggesting functional divergence of mTORC2 between mitosis and female meiosis. Based on the general function of mTORC2 in the organization of the actin cytoskeleton, we propose that mTORC1 controls spindle function during mitosis and meiosis, while mTORC2 contributes to actin-dependent asymmetric division during meiotic maturation in mice.
authors: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. kogayou8539@gmail.com
authors: Yuhei
authors: Y
authors: Kogasaka
authors: Yumi
authors: Y
authors: Hoshino
authors: Yuuki
authors: Y
authors: Hiradate
authors: Kentaro
authors: K
authors: Tanemura
authors: Eimei
authors: E
authors: Sato
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000378:metabolism; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D046912:Multiprotein Complexes / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D008941:Spindle Apparatus / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; C525637:rictor protein, mouse; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases