A5081018954- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Nerve injury and regeneration
- Signaling Pathways in Disease
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Lipid Membrane Structure and Behavior
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Autism Spectrum Disorder Research
- Bacterial Genetics and Biotechnology
- Ion Channels and Receptors
- Neuroendocrine regulation and behavior
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Retinal Development and Disorders
- Glycosylation and Glycoproteins Research
- Gene expression and cancer classification
- Pancreatic function and diabetes
Tokyo University of Science
2016-2025
RIKEN Center for Brain Science
2012-2024
The University of Tokyo
1992-2021
Japan Science and Technology Agency
2009-2021
Konami (United States)
2021
Kihara Institute for Biological Research
2021
Yokohama City University
2021
Kyoto University
2021
Weatherford College
2021
Kobe University
2021
Loss-of-function mutations in human SCN1A gene encoding Nav1.1 are associated with a severe epileptic disorder known as myoclonic epilepsy infancy. Here, we generated and characterized knock-in mouse line loss-of-function nonsense mutation the Scn1a gene. Both homozygous heterozygous mice developed seizures within first postnatal month. Immunohistochemical analyses revealed that, developing neocortex, was clustered predominantly at axon initial segments of parvalbumin-positive (PV)...
Additional subtypes of the inositol 1,4,5-trisphosphate (InsP3) receptor are expressed in a tissue-specific and developmentally specific manner. They differ from InsP3 structure previously reported two small variably spliced segments. One segment (SI) is located within binding site, whereas another (SII) near putative sites for phosphorylation ATP to modulate action on Ca2+ flux. Therefore, we speculate that selective use permits expression functionally distinct channels.
The neuronal Ca2+ signal is induced by a rise in the intracellular free concentration ([Ca2+]i), and thought to be important for higher brain function. Dynamic changes [Ca2+]i are affected spatial distributions of various Ca(2+)-increasing molecules (channels receptors). ryanodine receptor (RyR) an channel through which released from stores. To define contribution signaling via RyR channel, we examined type-specific gene expression rabbit situ hybridization histochemistry. was composed three...
Abstract: To clarify the mechanism of cerebellar development, we have cloned a gene, named zic, encoding zinc finger protein that is expressed abundantly in granule cells throughout development cerebellum. zic has significant homology to domain Caenorhabditis elegans tra1 Drosophila cubitus interruptus Dominant and human GLI oncogene. An situ hybridization study revealed showed restricted expression pattern their putative precursor cells. It also at an early embryonic stage dorsal half...
To define the structural determinants for inositol 1,4,5-trisphosphate (IP3) binding of type 1 receptor (IP3R1), we developed a means expressing N-terminal 734 amino acids IP3R1 (T734), which contain IP3 region, in Escherichia coli. The T734 protein expressed E. coli exhibited similar specificity and affinity as native IP3R from mouse cerebellum. Deletion mutagenesis, was serially deleted N terminus up to residue 215, markedly reduced activity. However, when little more toward C (to residues...
The inositol 1,4,5-trisphosphate receptor (IP3R) exists as a tetrameric complex to form functional 1,4,5-trisphosphate-gated Ca2+ channel. Molecular cloning studies have shown that there are at least three types of IP3R subunits, designated type 1, 2, and 3. levels expression subunits in various cell lines were investigated by Western blot analysis using type-specific antibodies against 15 C-terminal amino acids each subunit. We found all the expressed line examined, but their varied. To...
Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, its underlying molecular mechanisms remain unknown. Ca(2+)-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates exocytosis of dense-core vesicles, human CADPS2 located within autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor...
Ca 2+ -dependent activator protein for secretion 2 (CAPS2/CADPS2) is a secretory granule-associated that abundant at the parallel fiber terminals of granule cells in mouse cerebellum and involved release neurotrophin-3 (NT-3) brain-derived neurotrophic factor (BDNF), both which are required cerebellar development. The human homolog gene on chromosome 7 located within susceptibility locus 1 autism, disease characterized by several morphological abnormalities. Here we report CAPS2 knock-out...
Abstract Background Neuronal activity alters calcium ion (Ca 2+ ) dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model which expression inositol 1,4,5-trisphosphate absorbent, “IP 3 sponge”, attenuates astrocytic Ca signaling. Results Attenuated correlated with reduced coverage asymmetric synapses hippocampal CA1 region animals. The decreased ‘protection’ facilitated glutamate...
The homotetrameric complex of inositol 1,4,5-triphosphate (InsP3) receptors displays a Ca2+ release activity in response to InsP3 molecules. Structure-function relationships the mouse cerebellar receptor have been studied by analyses series internal deletion or C-terminal truncation mutant proteins expressed NG108-15 cells. Within large cytoplasmic portion receptor, approximately 650 N-terminal amino acids are highly conserved between and Drosophila, this region has critical sequences for...
We isolated a cDNA encoding an inositol 1,4,5-trisphosphate receptor (InsP3R) of Drosophila melanogaster. The predicted InsP3R (2,833 amino acids) has extensive sequence similarity to the mouse InsP3R. polypeptide encoded by was functionally expressed and showed characteristic InsP3-binding activity. gene is located at region 83A5-9 on third chromosome expresses throughout development but predominantly in adult. Localization mRNA adult tissues suggests strong expression retina antenna,...
To understand the molecular mechanism of ligand-induced gating inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)/Ca2+release channel, we analyzed channel properties deletion mutants retaining both IP3-binding and channel-forming domains IP3R1. Using intrinsically IP3R-deficient cells as host for expression, determined that six mutants, those lacking residues 1–223, 651–1130, 1267–2110, 1845–2042, 1845–2216, 2610–2748, did not exhibit any measurable Ca2+ release activity, whereas 1131–1379...