| Project/Area Number |
02044098
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research |
|---|
| Research Institution | Institute for Protein Research, Osaka University |
|---|
Principal Investigator |
MIKOSHIBA Katsuhiko Institute for Protein research, Osaka University, たんぱく質研究所, 教授 (30051840)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NIINOBE Michio Institute for Protein Research, Osaka University, 蛋白質研究所, 助手 (80135748)
IKENAKA kazuhiro Institute for Protein Research, Osaka University, 蛋白質研究所, 助教授 (00144527)
GUENET Jean-Louis Institut Pasteur (Paris), 教授
|
|---|
| Project Period (FY) |
1991
|
| Project Status |
Completed (Fiscal Year 1991)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | mouse mutant / cerebellum / calcium channel / endoplasmic reticulum / InsP_3 receptor or IP_3 receptor / InsP_3 (inositol trisphosphate) or IP_3 / morphogenesis / InsP_3レセプタ- / 染色体マッピング / 小脳プルキン工細胞 / カルシウムチャネル / 小胞体 / 中枢神経系 / 発生と分化 / in situ ハイブリダイゼ-ション |
|---|
| Research Abstract |
Inositol 1, 4, 5-trisphosphate (IP_3) is Produced through the activation of phosphoinositide (PI) tumover by the physiological action of hormones, neurotransmitters and growth factors, and functions as an intracellular second messenger. IP_3 binds to a specific IP_3 receptor that releases Ca^<2+> from intracellular store sites such as the endoplasmic reticulum (ER). The increase in [Ca^<2+>]_i probably modulates functions of various Ca_<2+>1-associated proteins, leading to a variety of cellular responses to extracellular stimuli.
The IP_3 receptor was originally identified as the glycosylated and phosphorylated protein P400 present in the cerebellum from normal mice but not from cerebellar Purkinje-celldeficient mutant mice. We purified the protein from mouse cerebellum, prepared monoclonal antibodies, and subcellularly localized the receptor mostly at the ER of Purkinje cells. Current recording experiments by reconstitution of the purified receptors in planner lipid bilayer represented that the receptor has an IP_3-induced cation selective ion channel activity that is enhanced in the presence of ATP. We isolated the cDNA from a cerebellar cDNA library. The structural analysis and functional expression of the IP_3 receptor cDNA indicated that the functional IP_3 receptor complex is a homotetramer : the pretomer (2749 amino acids) has a large N-terminal cytoplasmic region (83%) with a ligand (IP_3) -binding site (N-terminal 650 amino acids) and modulation sites for cAMP-dependent phosphorylation and ATP-binding, and a short C-teffninal transmembrane region involved in forming a Ca^<2+> channel pore. This characteristic structure is well-conserved in the recently-cloned Drosophila receptor homologue, as well. From regional distribution of the IP_3 receptor, we will discuss the functional role of IP_3/Ca^<2+> signalling in the central nervous system.
|
