Browse > Article

Expression of Gas6 Receptors, Tyro3, Axl, and Mertk, in Oocytes and Embryos and Effects of Mertk RNAi on the Oocyte Maturation  

Kim, Kyeoung-Hwa (Department of Biomedical Science, College of Life Science, CHA University, CHA Research Institute, Fertility Center, CHA General Hospital)
Lee, Sang-Eun (Department of Biomedical Science, College of Life Science, CHA University, CHA Research Institute, Fertility Center, CHA General Hospital)
Lee, Kyung-Ah (Department of Biomedical Science, College of Life Science, CHA University, CHA Research Institute, Fertility Center, CHA General Hospital)
Publication Information
Development and Reproduction / v.16, no.3, 2012 , pp. 195-204 More about this Journal
Abstract
Recently, we reported growth arrest-specific gene 6 (Gas6) as a new maternal effect gene (MEG), that expressed in the oocytes but functioned principally during embryogenesis. Gas6 RNAi-treated oocytes developed to metaphase II (MII) stage but they have affected M-phase promoting factor (MPF) activity and incurred abnormal pronuclear (PN) formation during fertilization. Gas6 is a ligand of TAM family members (Tyro3, Axl and Mertk) of receptor tyrosine kinase (RTK). Purpose of the present study was to evaluate the expression of Tyro3, Axl and Mertk transcripts in oocytes and early embryos. Expression of Gas6 and Mertk mRNA was detectable in oocytes and follicular cells, while Tyro3 and Axl mRNA was expressed only in follicular cells. Expression of Mertk mRNA was relatively constant during oocytes maturation and embryogenesis, but the other receptors, Tyro3 and Axl, were not expressed in oocytes and PN stage of embryos at all. Knockdown of Mertk mRNA and protein by using sequence-specific Mertk double strand RNA (dsRNA) did not affect oocytes maturation. In this case, however, contrary to the ligand Gas6 RNA interference (RNAi), MPF activity had not been changed by Mertk RNAi. Therefore, we concluded that the Gas6-Mertk signaling is not directly related to the oocyte maturation. It is still required to study further regarding the function of Mertk as the receptor of Gas6 during preimplantational early embryogenesis.
Keywords
Gas6 receptors; Tyro3; Axl; Mertk; RNA interference;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Allen MP, Zeng C, Schneider K, Xiong X, Meintzer MK, Bellosta P, Basilico C, Varnum B, Heidenreich KA, Wierman ME (1999) Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt. Mol Endocrinol 13:191-201.   DOI   ScienceOn
2 Binder MD, Xiao J, Kemper D, Ma GZ, Murray SS, Kilpatrick TJ (2011) Gas6 increases myelination by oligodendrocyted and its deficiency delays recovery following cuprizone-induced demyelination. PLoS One 10;6(3)e17727.   DOI   ScienceOn
3 Brunet S, Maro B (2005) Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space. Reproduction 130:801-811.   DOI   ScienceOn
4 Cavet ME, Smolock EM, Menon P, Konishi A, Korshunov VA, Berk BC (2010) Gas6-Axl pathway: the role of redox-dependent association of Axl with nonmuscle myosin IIB. Hypertension 56:105-111.   DOI   ScienceOn
5 Chen J, Carey K, Godowski PJ (1997) Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Oncogene 14:2033-2039.   DOI   ScienceOn
6 Cosemans JM, Van Kruchten R, Olieslagers S, Schugers LJ, Verheyen FK, Munnix IC, Waltenberger J, Angelilloscherrer A, Hoylaerts MF, Carmeliet P, Heemskerk JW (2010) Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization. J Thromb Haemost 8(8):1797-1808.   DOI   ScienceOn
7 Cox LJ, Larman MG, Saunders CM, Hashimoto K, Swann K, Lai FA (2002) Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers $Ca^{2+}$ oscillations, activation and development of mouse oocytes. Reproduction 124:611-623.   DOI   ScienceOn
8 Eppig JJ, Wigglesworth K (2000) Development of mouse and rat oocytes in chimeric reaggregated ovaries after interspecific exchange of somatic and germ cell components. Biol Reprod 63:1014-1023.   DOI   ScienceOn
9 Fulka J Jr, First NL, Moor RM (1998) Nuclear and cytoplasmic determinants involved in the regulation of mammalian oocyte maturation. Mol Hum Reprod 4: 41-49.   DOI   ScienceOn
10 Gandolfi TA, Gandolfi F (2001) The maternal legacy to the embryo: cytoplasmic components and their effects on early development. Theriogenology 55:1255-1276.   DOI   ScienceOn
11 Goruppi S, Ruaro E, Schneider C (1996) Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts. Oncogene 12:471-480.
12 Graham DK, Bowman GW, Dawson TL, Stanford WL, Earp HS, Snodgrass HR (1995) Cloning and developmental expression analysis of the murine c-mer tyrosine kinase. Oncogene 10:2349-2359.
13 Goruppi S, Ruaro E, Varnum B, Schneider C (1999) Gas6- mediated survival in NIH3T3 cells activates stress signalling cascade and is independent of Ras. Oncogene 18:4224-4236.   DOI   ScienceOn
14 Gosden RG (2002) Oogenesis as a foundation for embryogenesis. Mol Cell Endocrinol 186:149-153.   DOI   ScienceOn
15 Goudet G, Belin F, Bezard J, Gerard N (1998) Maturationpromoting factor (MPF) and mitogen activated protein kinase (MAPK) expression in relation to oocyte competence for in vitro maturation in the mare. Mol Hum Reprod 4:563-570.   DOI   ScienceOn
16 Graham DK, Dawson TL, Mullaney DL, Snodgrass HR, Earp HS (1994) Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ 5:647-657.
17 Greve JM, Wassarman PM (1985) Mouse egg extracellular coat is a matrix of interconnected filaments possessing a structural repeat. J Mol Biol 181:253-264.   DOI
18 Hegele-Hartung C, Kuhnke J, Lessl M, Grondahl C, Ottesen J, Beier Hm, Eisner S, Eichenlaub-Ritter U (1999) Nuclear and cytoplasmic maturation of mouse oocytes after treatment with synthetic meiosis-activating sterol in vitro. Biol Reprod 61:1362-1372.   DOI   ScienceOn
19 Jones KT (1998) $Ca^{2+}$ oscillations in the activation of the egg and development of the embryo in mammals. Int J Dev Biol 42:1-10.
20 Jones KT, Carroll J, Merriman JA, Whittingham D, Kono T (1995) Repetitive sperm-induced $Ca^{2+}$ transients in mouse oocytes are cell cycle dependent. Development 121:3259-3266.
21 Kim KH, Kim EY, Kim Y, Kim E, Lee HS, Yoon SY, Lee KA (2011) Gas6 downregulation impaired cytoplasmic maturation and pronuclear formation independent to MPF activity. PLoS one 6(8):e23304.   DOI   ScienceOn
22 Josefsberg Lb, Galiani D, Lazar S, Kaufman O, Seger R, Dekel N (2003) Maturation-promoting factor governs mitogen-activated protein kinase activation and interphase suppression during meiosis of rat oocytes. Biol Reprod 68:1282-1290.   DOI
23 Katagiri M, Hakeda Y, Chikazu D, Ogasawara T, Takato T, Kumegawa M, Nakamura K, Kawaguchi H (2001) Mechanism of stimulation of osteoclastic bone resorption through Gas6/Tyro3, a receptor tyrosine kinase signaling, in mouse osteoclasts. J Biol Chem 276:7376-7382.   DOI   ScienceOn
24 Kim KH, Kim EY, Lee KA (2008) SEBOX is essential for early embryogenesis at the two-cell stage in the mouse. Biol Reprod 79:1192-1201.   DOI   ScienceOn
25 Korshunov VA (2012) Axl-dependent signaling: a clinical update. Clin Sci 122(8):361-368.   DOI
26 Ledan E, Polanski Z, Terret ME, Maro B (2001) Meiotic maturation of the mouse oocyte requires an equilibrium between cyclin B synthesis and degradation. Dev Biol 232:400-413.   DOI   ScienceOn
27 Li R, Chen J, Hammonds G, Phillips H, Armanini M, Wood P, Bunge R, Godowski PJ, Sliwkowski MX, Mather JP (1996) Identification of Gas6 as a growth factor for human Schwann cells. J Neurosci 16:2012-2019.
28 Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993) The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 13:4976-4985.   DOI
29 Masui Y (2001) From oocyte maturation to the in vitro cell cycle: the history of discoveries of Maturation- Promoting Factor (MPF) and Cytostatic Factor (CSF). Differentiation 69:1-17.   DOI   ScienceOn
30 Marangos P, Fitzharris G, Carroll J (2003) $Ca^{2+}$ oscillations at fertilization in mammals are regulated by the formation of pronuclei. Development 130:1461-1472.   DOI   ScienceOn
31 Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1996) Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem 271:30022-30027.   DOI   ScienceOn
32 Nakano T, Higashino K, Kikuchi N, Kishino J, Nomura K, Fujita H, Ohara O, Arita H (1995) Vascular smooth muscle cell-derived, Gla-containing growth-potentiating factor for $Ca(^{2+})-mobilizing$-mobilizing growth factors. J Biol Chem 270:5702-5705.   DOI   ScienceOn
33 Nasr-Esfahani MH, Razavi S, Mardani M, Shirazi R, Javanmardi S (2007) Effects of failed oocyte activation and sperm protamine deficiency on fertilization post-ICSI. Reprod Biomed Online 14:422-429.   DOI   ScienceOn
34 Ohashi K, Mizuno K, Kuma K, Miyata T, Nakamura T (1994) Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain. Oncogene 9:699-705.
35 Ohashi K, Nagata K, Toshima J, Nakano T, Arita H, Tsuda H, Suzuki K, Mizuno K (1995) Stimulation of sky receptor tyrosine kinase by the product of growth arrest-specific gene 6. J Biol Chem 270:22681-22684.   DOI   ScienceOn
36 Prieto Al, Weber Jl, Lai C (2000) Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system. J Comp Neurol 425:295-314.   DOI   ScienceOn
37 Shao WH, Zhen Y, Eisenberg RA, Cohen PL (2009) The Mer receptor tyrosine kinase is expressed on discrete macrophage subpopulations and mainly uses Gas6 as its ligand for uptake of apoptotic cells. Clin Immunol 133:138-144.   DOI   ScienceOn
38 Png KJ, Halberg N, Yoshida M, Tavazoie SF (2011) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 14;481(7380): 190-194.   DOI   ScienceOn
39 Sainaghi PP, Castello L, Bergamasco L, Galletti M, Bellosta P, Avanzi GC (2005). Gas6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor. J Cell Physiol 204:36-44.   DOI   ScienceOn
40 Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney LM, Swann K, Lai FA (2002) PLC zeta: a sperm-specific trigger of $Ca(^{2+})$ oscillations in eggs and embryo development. Development 129:3533-3544.
41 Yoon SJ, Chung HM, Cha KY, Kim NH, Lee KA (2005) Identification of differential gene expression in germinal vesicle vs. metaphase II mouse oocytes by using annealing control primers. Fertil Steril 83 Suppl 1:1293-1296.   DOI
42 Yoon SJ, Kim EY, Kim YS, Lee HS, Kim KH, Bae J, Lee KA (2009) Role of Bcl2-like 10 (Bcl2l10) in regulating mouse oocyte maturation. Biol Reprod 81: 497-506.   DOI   ScienceOn
43 Zizzo G, Hilliard BA, Monestier M, Cohen PL (2012) Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol Aug:31.   DOI   ScienceOn