title: Muscle regulatory factors regulate T1R3 taste receptor expression.
abstract: T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic β-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan; Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka, Japan. Electronic address: r14kokabu@fa.kyu-dent.ac.jp.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kokabu
authors.affiliation: Department of Biomedical Science, Marian University College of Osteopathic Medicine, 3200 Cold Spring Rd, Indianapolis, IN, 46222, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lowery
authors.affiliation: Division of Anatomy, Department of Health Promotion, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toyono
authors.affiliation: Division of Anatomy, Department of Health Promotion, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Seta
authors.affiliation: Division of Physiology, Department of Health Promotion, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
authors.forename: Suzuro
authors.initials: S
authors.lastname: Hitomi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Enoki
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoda
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D018006:Myogenic Regulatory Factors; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1
keywords: MyoD; Myogenesis; Myogenin; Umami receptor