title: SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.
abstract: BACKGROUND
  SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there.
  
  
  RESULTS
  Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)gamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5)P(2), and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice.
  
  
  CONCLUSIONS
  Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Akieda-Asai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Zaima
authors.forename: Koji
authors.initials: K
authors.lastname: Ikegami
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kahyo
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yao
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hatanaka
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Rika
authors.initials: R
authors.lastname: Sugiyama
authors.forename: Takeaki
authors.initials: T
authors.lastname: Yokozeki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Morio
authors.initials: M
authors.lastname: Koike
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yamaza
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Song
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuno
authors.forename: Akiko
authors.initials: A
authors.lastname: Mizutani
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Michael W
authors.initials: MW
authors.lastname: McBurney
authors.forename: Leonard
authors.initials: L
authors.lastname: Guarente
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
mesh_terms: D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D018274:Electroporation; D005838:Genotype; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: D013972:Thyrotropin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D056564:Sirtuin 1; D008239:Lysine