| Co-Investigator(Kenkyū-buntansha) |
SENBA Emika Wakayama Prefectural Med.Sch.Anatomy, Professor, 医学部, 教授 (00135691)
YONEDA Yoshihiro Osaka Univ.Med.Sch.Anatomy, Professor, 医学部, 教授 (80191667)
FUJIMOTO Toyoshi GUNMA Univ.Med.Sch.Anatomy, Professor, 医学部, 教授 (50115929)
SAITO Naoaki Kobe Univ.Biosignal Center, Pharm.Professor, バイオシグナル研究センター, 教授 (60178499)
ABE Hiroshi Tokai Univ.Med.Sch., Morphology, Professor, 医学部, 教授 (40151104)
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| Research Abstract |
The expression and regulation of signal-related molecules were analyzed at levels of genes and proteins in cells in-vitro and in-vivo with regard to their relation to the plasma wembrane, cytoskeletons, cytoplasmic matrix and nucleus. Targeted molecules and structural elements analyzed in this study were the membranous caveolae, connexins. CD-38 molecule, membranous undercoats in the plasma membrane ; Ca/calmodulin-dependent protein kinase IV (CaMK-IV), diacylglycerol kinase (DGK), protein kinase C (PKC) and vesicle-associated small G-proteinin in the cytoplasmic matrix ; nuclear import factors and immediate early genes in the nucleus.
The sequestration of GPI-anchored proteins, glycosphingolipids and sphingomyelin in the caveolae were shown to be results of cross-linking, although the localization of caveolin there were constitutive. CD-38, a cell surface-antigen having an activity of cyclic ADP-ribose synthase, was localized in glia, but not neurons, suggesting a new way of functional
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exertion of cyclic ADP-ribose synthase in the neuroanl signal transduction. The localization of dystrophin in the membranous undercoat of muscle cells were clarified in details and its topographical relation to cytoskeletons and exoplasmic surface structures were shown in ultrastructure. The heterogeneity in molecular structure and localization was clarified for DGK,CaMK-IV and PKC,and the nuclear localization of DGK-IV and CaMK-IV was revealed. The identification of novel cytoplasmic components and their importance in the nuclear protein-import were clarified in cultured cells. In the nucleus in vivo, changes in the expression of several immediate early genes occurred after various exogenous stimuli such as pain. A novel immediately early gene was identified from the hippocampus, implicating its functional involvement in synaptic plasticity. A small G-protein, rab 12 is shown to be involved in the secretory vesicle transport in atrial muscle cells. In conclusion, all these findings are of extreme importance in understanding the signal transduction mechanism in relation to cellular ultrastructure. Less
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