Ionotropic glutamate receptor AMPA 1 is associated with ovulation rate.
Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system by opening ion channels upon the binding of glutamate. Despite the essential roles of glutamate in the control of reproduction and anterior pituitary hormone secretion, there is a limited understanding of how glutamate receptors control ovulation. Here we reveal the function of the ionotropic glutamate receptor AMPA-1 (GRIA1) in ovulation. Based on a genome-wide association study in Bos taurus, we found that ovulation rate is influenced by a variation in the N-terminal leucine/isoleucine/valine-binding protein (LIVBP) domain of GRIA1, in which serine is replaced by asparagine. GRIA1(Asn) has a weaker affinity to glutamate than GRIA1(Ser), both in Xenopus oocytes and in the membrane fraction of bovine brain. This single amino acid substitution leads to the decreased release of gonadotropin-releasing hormone (GnRH) in immortalized hypothalamic GT1-7 cells. Cows with GRIA1(Asn) have a slower luteinizing hormone (LH) surge than cows with GRIA1(Ser). In addition, cows with GRIA1(Asn) possess fewer immature ovarian follicles before superovulation and have a lower response to hormone treatment than cows with GRIA1(Ser). Our work identified that GRIA1 is a critical mediator of ovulation and that GRIA1 might be a useful target for reproductive therapy.
National Livestock Breeding Center, Nishigo, Japan.
Mayumi
M
Sugimoto
Shinji
S
Sasaki
Toshio
T
Watanabe
Shota
S
Nishimura
Atsushi
A
Ideta
Maya
M
Yamazaki
Keiko
K
Matsuda
Michisuke
M
Yuzaki
Kenji
K
Sakimura
Yoshito
Y
Aoyagi
Yoshikazu
Y
Sugimoto
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002417:Cattle; D002460:Cell Line; D033481:Chromosomes, Mammalian / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism; D010060:Ovulation / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D018698:Glutamic Acid; D007987:Gonadotropin-Releasing Hormone; D018091:Receptors, AMPA