Inositol 1,4,5-trisphosphate (IP3) receptors.
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Animals↗
Biomedical subjects
T Furuichi
Publications and source records attributed to T Furuichi.
The subtypes of the mouse inositol 1,4,5-trisphosphate receptor are expressed in a tissue-specific and developmentally specific manner.
Additional subtypes of the inositol 1,4,5-trisphosphate (InsP3) receptor are expressed in a tissue-specific and developmentally specific manner. They differ from the InsP3 receptor structure previously reported in two small variably spliced segments. One segment (SI) is located within the InsP3 binding site, whereas another segment (SII) is located near putative sites for phosphorylation and ATP binding to modulate InsP3 action on Ca2+ flux. Therefore, we speculate that selective use of InsP3 receptor subtypes permits a tissue-specific and developmentally specific expression of functionally distinct channels.
Aging↗
Structure-function relationships of the mouse inositol 1,4,5-trisphosphate receptor.
The homotetrameric complex of inositol 1,4,5-triphosphate (InsP3) receptors displays a Ca2+ release activity in response to InsP3 molecules. Structure-function relationships of the mouse cerebellar InsP3 receptor have been studied by analyses of a series of internal deletion or C-terminal truncation mutant proteins expressed in NG108-15 cells. Within the large cytoplasmic portion of the InsP3 receptor, approximately 650 N-terminal amino acids are highly conserved between mouse and Drosophila, and this region has the critical sequences for InsP3 binding that probably form the three-dimensionally restricted binding site. The N-terminal region of each InsP3 receptor subunit also binds one InsP3 molecule. Cross-linking experiments have revealed that InsP3 receptors are intermolecularly associated at the transmembrane domains and/or the successive C termini. The interaction between the receptor subunit and InsP3 may cause a conformational change in the tetrameric complex, resulting in the opening of Ca2+ channels.
Amino Acid Sequence↗
Primary structure and functional expression from complementary DNA of a brain calcium channel.
The primary structure of a voltage-dependent calcium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA. Calcium channel activity expressed from the cDNA is dramatically increased by coexpression of the alpha 2 and beta subunits, known to be associated with the dihydropyridine receptor. This channel is a high voltage-activated calcium channel that is insensitive both to nifedipine and to omega-conotoxin. We suggest that it is expressed predominantly in cerebellar Purkinje cells and granule cells.
Amino Acid Sequence↗
Primary structure and functional expression of the inositol 1,4,5-trisphosphate receptor, P400.
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Amino Acid Sequence↗
The inhibitory effects of oligonucleotides, complementary to Marek's disease virus mRNA transcribed from the BamHI-H region, on the proliferation of transformed lymphoblastoid cells, MDCC-MSB1.
An oligonucleotide complementary to the splice donor sequence of the 1.8 kb gene family produced from the BamHI-H region of Marek's disease virus (MDV) DNA inhibited the proliferation of the MDV-derived lymphoblastoid cell line, MDCC-MSB1 (MSB-1), but not that of the avian lymphoid leukosis-derived lymphoblastoid cell line, LSCC-BK3. Colony formation in soft agar was also inhibited by treatment of MSB-1 cells with the antisense oligonucleotide. It is hypothesized that expression of the 1.8 kb gene family produced from the BamHI-H region is directly associated with the maintenance of the tumorigenic state of transformed Marek's disease-derived lymphoblastoid cells.
Animals↗
Structure of the 68-kDa neurofilament gene and regulation of its expression.
The complete structure of the mouse 68-kDa neurofilament (NF-L) gene was elucidated. We cloned cDNAs corresponding to 3.5- and 2.3-kb NF-L mRNA, including their polyadenylation sites. Sequence analysis revealed that these NF-L mRNAs arose from the alternative use of two polyadenylation sites in exon 4. Promoter analysis using NF-L promoter-beta-galactosidase fusion plasmids determined regions responsible for its basic promoter activity, which were located between -328 and -36 base pairs from the transcription initiation site. These promoter fusion plasmids induced a significant level of beta-galactosidase in NF-nonproducing C6 cells as well as in NF-producing PC12h cells. The in vitro transcription assay using HeLa cell extract also showed that this promoter exhibited strong transcriptional activity. Little difference in NF-L mRNA stability was observed between the two cells. However, nuclear run-off assay revealed that the NF-L gene was not transcribed in NF-nonproducing C6 cells. These data suggest that the strong promoter activity of the NF-L gene is repressed in vivo at the transcription initiation level in a tissue-specific manner.
Animals↗
Isolation of complementary DNAs encoding a cerebellum-enriched nuclear factor I family that activates transcription from the mouse myelin basic protein promoter.
A nuclear factor I (NFI) binding sequence in the myelin basic protein (MBP) promoter is required for brain-specific transcription. In the present study, we isolated multiple cDNAs encoding a family of NFI, NFI-B, from mouse brain cDNA libraries. These clones contain unique nucleotide sequences at their 5', 3', or middle portions, presumably as a result of alternative splicing. The entire sequence of NFI-B suggests that NFI-B is a mouse counterpart of NFI-L, which was previously isolated from rat liver. NFI-B is highly enriched in the cerebellum, in contrast with a ubiquitous NFI, CTF/NF-I. NFI-B proteins translated in vitro could bind to the MBP NFI site. Furthermore, we demonstrated by transfection experiments that NFI-B activated transcription from transfected MBP promoter in neuronal/glial NG108-15 cells.
Amino Acid Sequence↗
Distribution of inositol 1,4,5-trisphosphate receptor mRNA in mouse tissues.
Northern blot analysis demonstrated that the concentration of inositol 1,4,5-triphosphate (IP3) receptor mRNA was greatest in cerebellar tissue. Moderate amounts of IP3 mRNA were present in brain tissue without cerebellum and tissue of the thymus, heart, lung, liver, spleen, kidney, and uterus. Small amounts of IP3 receptor mRNA were observed in skeletal muscle and testicular tissue. Regional distribution of IP3 mRNA in various tissues was also examined by in situ hybridization. A considerable amount of IP3 receptor mRNA was located in smooth muscle cells, such as those of the arteries, bronchioles, oviduct and uterus. In addition, secondary oocytes surrounded by Graafian follicles in the ovary were found to have large amounts of IP3 receptor mRNA. The present studies suggest a functional importance of the IP3 second-messenger system in these cell types.
Animals↗
Expressed cerebellar-type inositol 1,4,5-trisphosphate receptor, P400, has calcium release activity in a fibroblast L cell line.
P400, inositol 1,4,5-trisphosphate receptor (InsP3-R), is a key protein to understanding the mechanisms of inositol 1,4,5-trisphosphate (InsP3)-mediated Ca2+ mobilization. We obtained the cerebellar-type P400/InsP3-R cDNA and generated an L cell transfectant (L15) that produces cDNA-derived P400/InsP3-R. In membranes, this protein displays high affinity, specificity, and capacity for InsP3, as does the cerebellar P400/InsP3-R. InsP3 can also induce greater 45Ca2+ release from the membrane vesicles of L15 cells than from those of control L cells. These results provide direct evidence that the cDNA-derived P400/InsP3-R protein is actually involved in physiological Ca2+ mobilization, through binding to InsP3 molecules in the same manner as the cerebellar P400/InsP3-R.
Animals↗
Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400.
Cloning and expression of functional P400 protein from cerebellar Purkinje neurons shows that this protein is a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
Amino Acid Sequence↗
Nucleotide sequence of cDNA encoding P400 protein in the mouse cerebellum.
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Animals↗
Statistical approach towards point sources of groundwater pollution with tetrachloroethylene: a field study.
Tetrachloroethylene contamination of well water occurred in a primarily residential area. To search for point source(s) of tetrachloroethylene contamination, 91 water samples were collected on three separate occasions from 41 shallow wells scattered in the areas. Three methods of groundwater level analysis (limited to 30 wells), cluster analysis of water quality indicators and contour drawing of tetrachloroethylene concentrations were applied. The former two analyses showed that the pollution took place in aquifers of two terraces out of the three in the polluted area. The contour mapping demonstrated the presence of three spots of suspected pollution sources as the estimated points of highest tetrachloroethylene concentrations. The available information suggested the existence of a facility with possible use of tetrachloroethylene in the past.
Hydrocarbons, Chlorinated↗
Myelin proteolipid protein gene structure and its regulation of expression in normal and jimpy mutant mice.
The mouse proteolipid protein (PLP) gene was cloned into the lambda bacteriophage Charon 4A. The organization and the nucleotide sequence of the exons of the mouse PLP gene were quite similar to those of their human counterparts, consisting of seven exons. The transcription of the PLP gene started from multiple sites. There was a unique sequence tandemly repeated four times, sharing homology with the herpes simplex virus DR2 sequence, upstream from the transcribed region. Expression of the myelin basic protein (MBP) is also restricted to the oligodendrocytes in the central nervous system as is the PLP expression. Homology search against the mouse MBP gene revealed that several boxes in the 5'-flanking region of PLP show a high degree of homology with the sequence present in the MBP 5'-flanking region, possibly of importance in the concomitant expression of both genes in the central nervous system. PLP-mRNA in jimpy mutant mice does not contain exon 5 and its content is greatly reduced. We analyzed the jimpy PLP-mRNA and showed that the transcription initiated from the same sites as those in normal mice. Cloning and sequencing of the 5'-flanking region of the jimpy PLP gene revealed that there were no mutations in the promoter region of the jimpy PLP gene. Therefore, it is likely that a mutation, presumably existing within the jimpy PLP gene, caused the skipping of exon 5 and directly affected the mRNA level.
Amino Acid Sequence↗
Mutations that affect production of branched RNA-linked msDNA in Myxococcus xanthus.
A deletion mutation of the gene (msd-msr) for the branched RNA-linked msDNA of Myxococcus xanthus was constructed by replacing the chromosomal 0.7-kilobase (kb) SmaI-XhoI fragment encompassing msd-msr with a 1.4-kb fragment carrying a gene for kanamycin resistance. It was found that this deletion strain (delta msSX) could not produce msDNA, although it still contained another species of msDNA, mrDNA (msDNA, reduced size). No apparent differences between delta msSX and the wild-type strain were observed in terms of cell growth, morphogenesis, fruiting-body formation, or motility. Both a deletion mutation at the region 100 base pairs upstream of msd and an insertion mutation at a site 500 base pairs upstream of msd showed a significant reduction of msDNA production, indicating that there is a cis- or trans-acting positive element in this region. When the 3.5-kb BamHI fragment carrying msd-msr from Stigmatella aurantiaca was inserted into the M. xanthus chromosome, the S. aurantiaca msDNA was found to be produced in M. xanthus.
Chromosome Deletion↗
Structure of msDNA from Myxococcus xanthus: evidence for a long, self-annealing RNA precursor for the covalently linked, branched RNA.
The branched RNA (msdRNA) of M. xanthus consists of 77 bases. The 20th rG residue is linked to the 5' end of msDNA, consisting of 162 bases, by a 2', 5' phosphodiester linkage. The msdRNA coding region is located on the chromosome in the opposite orientation to the msDNA coding region, with the 3' ends overlapping by eight bases. S1 nuclease mapping experiments indicate that the primary product of msdRNA is much longer at both the 5' and 3' ends (approximately 375 bases). Because of homologous sequences upstream of the msdRNA and msDNA coding regions, the precursor RNA molecule is considered to form an extremely stable stem-and-loop structure (delta G = -210 kcal). We propose a novel mechanism of DNA synthesis in which the stem-and-loop structure serves as a primer as well as a template to form the branched RNA-linked msDNA.
Base Sequence↗
Branched RNA covalently linked to the 5' end of a single-stranded DNA in Stigmatella aurantiaca: structure of msDNA.
Stigmatella aurantiaca is a gliding, gram-negative bacterium that shows a spectacular fruiting body formation upon starvation of nutrient. This bacterium was found to contain approximately 500 copies per cell of a short single-stranded linear DNA (multicopy single-stranded DNA: msDNA). The primary structure of msDNA was determined and found to consist of 162 or 163 deoxyribonucleotides. Its unique chromosomal gene was cloned and sequenced. The msDNA was found to be attached to a branched RNA by its 5' end. Structural analysis of the branched RNA revealed that it consists of a triribonucleotide, 5'A-G-(C or U)3', and that msDNA is branched out from the 2' position of the rG residue forming a 2', 5' phosphodiester linkage with the dC residue at the 5' end of msDNA.
Base Sequence↗
Biosynthesis and structure of stable branched RNA covalently linked to the 5' end of multicopy single-stranded DNA of Stigmatella aurantiaca.
Stigmatella aurantiaca, a gram-negative bacterium, contains approximately 500 copies per cell of a short single-stranded linear DNA (multicopy single-stranded DNA: msDNA). This DNA is attached to a branched RNA (msdRNA) by its 5' end. The entire sequence of msdRNA was determined and found to consist of 76 bases. The msDNA is linked at the 19th G residue of msdRNA by a 2', 5' phosphodiester linkage. The coding region for msdRNA (msr) is located downstream of the coding region for msDNA (msd). These coding regions exist in opposite orientation with respect to each other and overlap by 8 bases at their 3' ends. Biosynthesis of RNA-linked msDNA was characterized and mechanisms of synthesis are proposed.
Base Sequence↗