| First Author | Kawaai K | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 17 | Pages | 5515-20 |
| PubMed ID | 25922519 | Mgi Jnum | J:319100 |
| Mgi Id | MGI:6862720 | Doi | 10.1073/pnas.1503310112 |
| Citation | Kawaai K, et al. (2015) IRBIT regulates CaMKIIalpha activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. Proc Natl Acad Sci U S A 112(17):5515-20 |
| abstractText | 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 (CaMKIIalpha) as an IRBIT-interacting molecule in the central nervous system. IRBIT binds to and suppresses CaMKIIalpha kinase activity by inhibiting the binding of calmodulin to CaMKIIalpha. 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 CaMKIIalpha, which affects TH activity, was significantly increased in the ventral tegmental area of IRBIT-deficient mice. We concluded that IRBIT suppresses CaMKIIalpha activity and contributes to catecholamine homeostasis through TH phosphorylation. |
