Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca2+ signaling |
| |
Authors: | Hattori Mitsuharu Suzuki Akinobu Z Higo Takayasu Miyauchi Hiroshi Michikawa Takayuki Nakamura Takeshi Inoue Takafumi Mikoshiba Katsuhiko |
| |
Institution: | Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8, Hon-machi, Kawaguchi, Saitama 332-0012, Japan. mhattori@ims.u-tokyo.ac.jp |
| |
Abstract: | Three subtypes of inositol 1,4,5-trisphosphate receptor (IP(3)R1, IP(3)R2, and IP(3)R3) Ca(2+) release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca(2+) signaling, such as Ca(2+) oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP(3)R1 and IP(3)R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca(2+) signaling patterns. Knockdown of IP(3)R1 significantly decreases total Ca(2+) signals and terminates Ca(2+) oscillations. Conversely, knockdown of IP(3)R3 leads to more robust and long lasting Ca(2+) oscillations than in controls. Effects of IP(3)R3 knockdown are surprisingly similar in COS-7 cells that predominantly (>90% of total IP(3)R) express IP(3)R3, suggesting that IP(3)R3 functions as an anti-Ca(2+)-oscillatory unit without contributing to peak amplitude of Ca(2+) signals, irrespective of its relative expression level. Therefore, differential expression of the IP(3)R subtype is critical for various forms of Ca(2+) signaling, and, particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca(2+) oscillations. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|