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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5515-5520
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number17
DOIs
Publication statusPublished - 2015 Apr 28

Keywords

  • CaMKIIα
  • Catecholamine
  • Hyperactivity
  • IRBIT

ASJC Scopus subject areas

  • General

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