SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals
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 ex...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/60353 https://orcid.org/0000-0003-4064-2510 |
| _version_ | 1826210226290819072 |
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| author | Guarente, Leonard Pershing Akieda-Asai, Sayaka Zaima, Nobuhiro Ikegami, Koji Kahyo, Tomoaki Yao, Ikuko Hatanaka, Takahiro Iemura, Shun-ichiro Sugiyama, Rika Yokozeki, Takeaki Eishi, Yoshinobu Koike, Morio Ikeda, Kyoji Chiba, Takuya Yamaza, Haruyoshi Shimokawa, Isao Song, Si-Young Matsuno, Akira Mizutani, Akiko Sawabe, Motoji Chao, Moses V. Tanaka, Masashi Kanaho, Yasunori Natsume, Tohru Sugimura, Haruhiko Date, Yukari McBurney, Michael W. Setou, Mitsutoshi |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Guarente, Leonard Pershing Akieda-Asai, Sayaka Zaima, Nobuhiro Ikegami, Koji Kahyo, Tomoaki Yao, Ikuko Hatanaka, Takahiro Iemura, Shun-ichiro Sugiyama, Rika Yokozeki, Takeaki Eishi, Yoshinobu Koike, Morio Ikeda, Kyoji Chiba, Takuya Yamaza, Haruyoshi Shimokawa, Isao Song, Si-Young Matsuno, Akira Mizutani, Akiko Sawabe, Motoji Chao, Moses V. Tanaka, Masashi Kanaho, Yasunori Natsume, Tohru Sugimura, Haruhiko Date, Yukari McBurney, Michael W. Setou, Mitsutoshi |
| author_sort | Guarente, Leonard Pershing |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:46:26Z |
| format | Article |
| id | mit-1721.1/60353 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:46:26Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/603532022-10-01T22:21:40Z SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals Guarente, Leonard Pershing Akieda-Asai, Sayaka Zaima, Nobuhiro Ikegami, Koji Kahyo, Tomoaki Yao, Ikuko Hatanaka, Takahiro Iemura, Shun-ichiro Sugiyama, Rika Yokozeki, Takeaki Eishi, Yoshinobu Koike, Morio Ikeda, Kyoji Chiba, Takuya Yamaza, Haruyoshi Shimokawa, Isao Song, Si-Young Matsuno, Akira Mizutani, Akiko Sawabe, Motoji Chao, Moses V. Tanaka, Masashi Kanaho, Yasunori Natsume, Tohru Sugimura, Haruhiko Date, Yukari McBurney, Michael W. Setou, Mitsutoshi Massachusetts Institute of Technology. Department of Biology Guarente, Leonard Pershing Guarente, Leonard Pershing 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. Mitsubishi Institute of Life Sciences Japan Society for the Promotion of Science. (WAKATE S grant) 2010-12-21T22:25:02Z 2010-12-21T22:25:02Z 2010-07 2010-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/60353 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. https://orcid.org/0000-0003-4064-2510 en_US http://dx.doi.org/10.1371/journal.pone.0011755 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Guarente, Leonard Pershing Akieda-Asai, Sayaka Zaima, Nobuhiro Ikegami, Koji Kahyo, Tomoaki Yao, Ikuko Hatanaka, Takahiro Iemura, Shun-ichiro Sugiyama, Rika Yokozeki, Takeaki Eishi, Yoshinobu Koike, Morio Ikeda, Kyoji Chiba, Takuya Yamaza, Haruyoshi Shimokawa, Isao Song, Si-Young Matsuno, Akira Mizutani, Akiko Sawabe, Motoji Chao, Moses V. Tanaka, Masashi Kanaho, Yasunori Natsume, Tohru Sugimura, Haruhiko Date, Yukari McBurney, Michael W. Setou, Mitsutoshi SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title_full | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title_fullStr | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title_full_unstemmed | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title_short | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals |
| title_sort | sirt1 regulates thyroid stimulating hormone release by enhancing pip5kγ subscript gamma activity through deacetylation of specific lysine residues in mammals |
| url | http://hdl.handle.net/1721.1/60353 https://orcid.org/0000-0003-4064-2510 |
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