SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma 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 expre...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2909264?pdf=render |
| _version_ | 1819129446225936384 |
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| author | Sayaka Akieda-Asai Nobuhiro Zaima Koji Ikegami Tomoaki Kahyo Ikuko Yao Takahiro Hatanaka Shun-Ichiro Iemura Rika Sugiyama Takeaki Yokozeki Yoshinobu Eishi Morio Koike Kyoji Ikeda Takuya Chiba Haruyoshi Yamaza Isao Shimokawa Si-Young Song Akira Matsuno Akiko Mizutani Motoji Sawabe Moses V Chao Masashi Tanaka Yasunori Kanaho Tohru Natsume Haruhiko Sugimura Yukari Date Michael W McBurney Leonard Guarente Mitsutoshi Setou |
| author_facet | Sayaka Akieda-Asai Nobuhiro Zaima Koji Ikegami Tomoaki Kahyo Ikuko Yao Takahiro Hatanaka Shun-Ichiro Iemura Rika Sugiyama Takeaki Yokozeki Yoshinobu Eishi Morio Koike Kyoji Ikeda Takuya Chiba Haruyoshi Yamaza Isao Shimokawa Si-Young Song Akira Matsuno Akiko Mizutani Motoji Sawabe Moses V Chao Masashi Tanaka Yasunori Kanaho Tohru Natsume Haruhiko Sugimura Yukari Date Michael W McBurney Leonard Guarente Mitsutoshi Setou |
| author_sort | Sayaka Akieda-Asai |
| collection | DOAJ |
| 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)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. |
| first_indexed | 2024-12-22T08:43:51Z |
| format | Article |
| id | doaj.art-058e2cab7c54476c87f498a588a61b8b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T08:43:51Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-058e2cab7c54476c87f498a588a61b8b2022-12-21T18:32:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0157e1175510.1371/journal.pone.0011755SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.Sayaka Akieda-AsaiNobuhiro ZaimaKoji IkegamiTomoaki KahyoIkuko YaoTakahiro HatanakaShun-Ichiro IemuraRika SugiyamaTakeaki YokozekiYoshinobu EishiMorio KoikeKyoji IkedaTakuya ChibaHaruyoshi YamazaIsao ShimokawaSi-Young SongAkira MatsunoAkiko MizutaniMotoji SawabeMoses V ChaoMasashi TanakaYasunori KanahoTohru NatsumeHaruhiko SugimuraYukari DateMichael W McBurneyLeonard GuarenteMitsutoshi SetouBACKGROUND: 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.http://europepmc.org/articles/PMC2909264?pdf=render |
| spellingShingle | Sayaka Akieda-Asai Nobuhiro Zaima Koji Ikegami Tomoaki Kahyo Ikuko Yao Takahiro Hatanaka Shun-Ichiro Iemura Rika Sugiyama Takeaki Yokozeki Yoshinobu Eishi Morio Koike Kyoji Ikeda Takuya Chiba Haruyoshi Yamaza Isao Shimokawa Si-Young Song Akira Matsuno Akiko Mizutani Motoji Sawabe Moses V Chao Masashi Tanaka Yasunori Kanaho Tohru Natsume Haruhiko Sugimura Yukari Date Michael W McBurney Leonard Guarente Mitsutoshi Setou SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. PLoS ONE |
| title | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. |
| title_full | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. |
| title_fullStr | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. |
| title_full_unstemmed | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. |
| title_short | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. |
| title_sort | sirt1 regulates thyroid stimulating hormone release by enhancing pip5kgamma activity through deacetylation of specific lysine residues in mammals |
| url | http://europepmc.org/articles/PMC2909264?pdf=render |
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