title: Epidermal Growth Factor-Mobilized Intracellular Calcium of Cumulus Cells Decreases Natriuretic Peptide Receptor 2 Affinity for Natriuretic Peptide Type C and Induces Oocyte Meiotic Resumption in the Mouse.
abstract: Natriuretic peptide type C (NPPC) activation of the guanylyl cyclase-linked natriuretic peptide receptor (NPR) 2 maintains oocyte meiotic arrest. Luteinizing hormone (LH)-dependent epidermal growth factor (EGF) receptor signaling elevates calcium of cumulus cells to inactivate NPR2, resulting in meiotic resumption. This study investigated the regulatory mechanism of calcium on NPR2 inactivation. In mouse ovarian follicles, LH, through the activation of EGF receptor, significantly elevated calcium levels in cumulus cells, but decreased the binding affinity of NPR2 for NPPC. In cultured cumulus-oocyte complexes, the activation of EGF receptor by EGF mobilized intracellular calcium of cumulus cells to decrease NPR2 affinity and cGMP levels, resulting in meiotic resumption. However, hormone treatments had not changed NPR2 protein levels. In addition, the removal of magnesium ions from the medium decreased the binding affinity of NPR2 for NPPC, resulting in a decrease in cGMP levels and meiotic resumption. It is concluded that magnesium ions are required to maintain functional NPR2, and that LH-dependent EGF receptor signaling mobilizes intracellular calcium of cumulus cells to reduce NPPC-NPR2 interaction that is required for meiotic resumption.
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Hao
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Kong
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
authors.affiliation: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China zmeijia@cau.edu.cn.
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D008274:Magnesium / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D002118:Calcium; D004815:Epidermal Growth Factor; D008274:Magnesium; D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B
keywords: affinity; calcium; epidermal growth factor; meiosis; natriuretic peptide receptor 2