最先端研究セミナー

担当分野：遺伝子機能応用学分野　甲斐（内線：4405）

Abstract:

Trimeric intracellular cation (TRIC) channel subtypes, namely TRIC-A and TRIC-B, form homo trimeric complexes with a bullet-like structure to function as counter-ion movements coupled with Ca²⁺ release from the endo/sarcoplasmic reticulum. TRIC-A channels abundantly expressed in excitable tissues including brain and each muscle, whereas TRIC-B channels are ubiquitously detected throughout excitable and non-excitable cell types. Knockout mice lacking both TRIC-A and TRIC-B channels suffer embryonic cardiac failure, and the mutant cardiomyocytes show compromised ryanodine receptor (RyR)-mediated Ca²⁺ release (1). Though Tric-a-knockout mice are normal in terms of growth, the mice developed hypertension even at young-adult stage (2, 3). On the other hand, Tric-b-knockout mice exhibit neonatal lethality due to respiratory failure (4). Recently, we found that Tric-b-knockout mice exhibit poor bone ossification and thus serve as an OI-model animal (5). Based on our observations in knockout mice, TRIC channels seem to mediate, in part, counter-ion movements to support efficient Ca²⁺ release from the endo/sarcoplasmic reticulum. In the seminar, I would like to discuss functional role of TRIC channels and future plan on TRIC channel study.

References

1. Yazawa et al. TRIC channels are essential for Ca²⁺ handling in intracellular stores. Nature 448, 78-82, 2007.
2. Yamazaki D et al. TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance. Cell Metab. 14, 231-41, 2011.
3. Tao et al. Facilitated hyperpolarization signaling in vascular smooth muscle-overexpressing TRIC-A channels. J Biol Chem. 288, 15581-9, 2013.
4. Yamazaki D et al. Essential role of the TRIC-B channel in Ca²⁺ handling of alveolar epithelial cells and in perinatal lung maturation. Development 136, 2355-61, 2009.
5. Zhao et al. Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization. Sci Signal. 9, ra49, 2016.

※　詳細はこちらから