Ontology highlight
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.Methodology/principal findings
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/significance
Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.
SUBMITTER: Akieda-Asai S
PROVIDER: S-EPMC2909264 | biostudies-literature | 2010 Jul
REPOSITORIES: biostudies-literature
Akieda-Asai Sayaka S Zaima Nobuhiro N Ikegami Koji K Kahyo Tomoaki T Yao Ikuko I Hatanaka Takahiro T Iemura Shun-Ichiro S Sugiyama Rika R Yokozeki Takeaki T Eishi Yoshinobu Y Koike Morio M Ikeda Kyoji K Chiba Takuya T Yamaza Haruyoshi H Shimokawa Isao I Song Si-Young SY Matsuno Akira A Mizutani Akiko A Sawabe Motoji M Chao Moses V MV Tanaka Masashi M Kanaho Yasunori Y Natsume Tohru T Sugimura Haruhiko H Date Yukari Y McBurney Michael W MW Guarente Leonard L Setou Mitsutoshi M
PloS one 20100723 7
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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. Usin ...[more]