IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation

Katsuhiro Kawaai, Akihiro Mizutani, Hirotaka Shoji, Naoko Ogawa, Etsuko Ebisui, Yukiko Kuroda, Shigeharu Wakana, Tsuyoshi Miyakawa, Chihiro Hisatsune, Katsuhiko Mikoshiba

研究成果: Article

19 引用 (Scopus)

抄録

Inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with IP3 (IRBIT) contributes to various physiological events (electrolyte transport and fluid secretion, mRNA polyadenylation, and the maintenance of genomic integrity) through its interaction with multiple targets. However, little is known about the physiological role of IRBIT in the brain. Here we identified calcium calmodulin-dependent kinase II alpha (CaMKIIα) as an IRBIT-interacting molecule in the central nervous system. IRBIT binds to and suppresses CaMKIIα kinase activity by inhibiting the binding of calmodulin to CaMKIIα. In addition, we show that mice lacking IRBIT present with elevated catecholamine levels, increased locomotor activity, and social abnormalities. The level of tyrosine hydroxylase (TH) phosphorylation by CaMKIIα, which affects TH activity, was significantly increased in the ventral tegmental area of IRBIT-deficient mice. We concluded that IRBIT suppresses CaMKIIα activity and contributes to catecholamine homeostasis through TH phosphorylation.

元の言語English
ページ(範囲)5515-5520
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
112
発行部数17
DOI
出版物ステータスPublished - 28-04-2015

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Calcium-Calmodulin-Dependent Protein Kinases
Tyrosine 3-Monooxygenase
Catecholamines
Homeostasis
Phosphorylation
Inositol 1,4,5-Trisphosphate Receptors
Fluids and Secretions
Ventral Tegmental Area
Polyadenylation
Calmodulin
Locomotion
Electrolytes
Carrier Proteins
Phosphotransferases
Central Nervous System
Maintenance
Calcium
Messenger RNA
Brain

All Science Journal Classification (ASJC) codes

  • General

これを引用

Kawaai, Katsuhiro ; Mizutani, Akihiro ; Shoji, Hirotaka ; Ogawa, Naoko ; Ebisui, Etsuko ; Kuroda, Yukiko ; Wakana, Shigeharu ; Miyakawa, Tsuyoshi ; Hisatsune, Chihiro ; Mikoshiba, Katsuhiko. / IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. :: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; 巻 112, 番号 17. pp. 5515-5520.
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abstract = "Inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with IP3 (IRBIT) contributes to various physiological events (electrolyte transport and fluid secretion, mRNA polyadenylation, and the maintenance of genomic integrity) through its interaction with multiple targets. However, little is known about the physiological role of IRBIT in the brain. Here we identified calcium calmodulin-dependent kinase II alpha (CaMKIIα) as an IRBIT-interacting molecule in the central nervous system. IRBIT binds to and suppresses CaMKIIα kinase activity by inhibiting the binding of calmodulin to CaMKIIα. In addition, we show that mice lacking IRBIT present with elevated catecholamine levels, increased locomotor activity, and social abnormalities. The level of tyrosine hydroxylase (TH) phosphorylation by CaMKIIα, which affects TH activity, was significantly increased in the ventral tegmental area of IRBIT-deficient mice. We concluded that IRBIT suppresses CaMKIIα activity and contributes to catecholamine homeostasis through TH phosphorylation.",
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IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. / Kawaai, Katsuhiro; Mizutani, Akihiro; Shoji, Hirotaka; Ogawa, Naoko; Ebisui, Etsuko; Kuroda, Yukiko; Wakana, Shigeharu; Miyakawa, Tsuyoshi; Hisatsune, Chihiro; Mikoshiba, Katsuhiko.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 112, 番号 17, 28.04.2015, p. 5515-5520.

研究成果: Article

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AU - Kawaai, Katsuhiro

AU - Mizutani, Akihiro

AU - Shoji, Hirotaka

AU - Ogawa, Naoko

AU - Ebisui, Etsuko

AU - Kuroda, Yukiko

AU - Wakana, Shigeharu

AU - Miyakawa, Tsuyoshi

AU - Hisatsune, Chihiro

AU - Mikoshiba, Katsuhiko

PY - 2015/4/28

Y1 - 2015/4/28

N2 - Inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with IP3 (IRBIT) contributes to various physiological events (electrolyte transport and fluid secretion, mRNA polyadenylation, and the maintenance of genomic integrity) through its interaction with multiple targets. However, little is known about the physiological role of IRBIT in the brain. Here we identified calcium calmodulin-dependent kinase II alpha (CaMKIIα) as an IRBIT-interacting molecule in the central nervous system. IRBIT binds to and suppresses CaMKIIα kinase activity by inhibiting the binding of calmodulin to CaMKIIα. In addition, we show that mice lacking IRBIT present with elevated catecholamine levels, increased locomotor activity, and social abnormalities. The level of tyrosine hydroxylase (TH) phosphorylation by CaMKIIα, which affects TH activity, was significantly increased in the ventral tegmental area of IRBIT-deficient mice. We concluded that IRBIT suppresses CaMKIIα activity and contributes to catecholamine homeostasis through TH phosphorylation.

AB - Inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with IP3 (IRBIT) contributes to various physiological events (electrolyte transport and fluid secretion, mRNA polyadenylation, and the maintenance of genomic integrity) through its interaction with multiple targets. However, little is known about the physiological role of IRBIT in the brain. Here we identified calcium calmodulin-dependent kinase II alpha (CaMKIIα) as an IRBIT-interacting molecule in the central nervous system. IRBIT binds to and suppresses CaMKIIα kinase activity by inhibiting the binding of calmodulin to CaMKIIα. In addition, we show that mice lacking IRBIT present with elevated catecholamine levels, increased locomotor activity, and social abnormalities. The level of tyrosine hydroxylase (TH) phosphorylation by CaMKIIα, which affects TH activity, was significantly increased in the ventral tegmental area of IRBIT-deficient mice. We concluded that IRBIT suppresses CaMKIIα activity and contributes to catecholamine homeostasis through TH phosphorylation.

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