SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals
Name
Akieda-Asai-2010-SIRT1 Regulates Thyr.pdf
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Author(s)
Guarente, Leonard Pershing
Akieda-Asai, Sayaka
Zaima, Nobuhiro
Ikegami, Koji
Kahyo, Tomoaki
Yao, Ikuko
Hatanaka, Takahiro
Iemura, Shun-ichiro
Sugiyama, Rika
Yokozeki, Takeaki
Date Issued
July 2010
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Akieda-Asai, Sayaka et al. “SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals.” Ed. Mikhail V. Blagosklonny. PLoS ONE 5.7 (2010): e11755.
Version
Final published version
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)γ[subscript gamma] was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ[subscript gamma] and enhanced PIP5Kγ[subscript gamma] enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ[subscript gamma] knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P[subscript 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-PIP5Kγ[subscript gamma] pathway is important for regulating the metabolism of the whole body.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0011755
