PubMed HealthSearch

Biomedical subjects

T Yamamori

Publications and source records attributed to T Yamamori.

At least 19 recordsLinked to original sources

Interaction of HPC-1/syntaxin 1A with the cytoskeletal protein, tubulin.

It is believed that HPC-1/syntaxin 1A regulates the intracellular membrane transport. We found a possible tubulin binding motif like sequence in residues 89 approximately 106 of HPC-1/syntaxin 1A. To determine whether or not HPC-1/syntaxin 1A binds to tubulin, we performed in vitro binding studies. We showed that both the rat brain and recombinant HPC-1/syntaxin 1A bound to tubulin in vitro. Competition experiments with synthetic peptides revealed that HPC-1/syntaxin 1A bound to tubulin at residues 89 approximately 106 which were supposed to constitute the tubulin binding consensus sequence.

Amino Acid Sequence

Jun-B expression in Purkinje cells by conjunctive stimulation of climbing fibre and AMPA.

Co-application of alpha-amino-3-hydro-5-methyl-4-isoxazole-propionate (AMPA) and 8-bromo cGMP (8-Br-cGMP) which cause long-term desensitization also induces c-Fos and Jun-B expression in Purkinje cells of cerebellar slices [Nakazawa K, Karachot L, Nakabeppu Y et al. NeuroReport 4, 1275-1278 (1993)]. Here, we report an increased local induction of Jun-B immunoreactivity in Purkinje cells in vivo when electrical stimulation of the inferior olive nucleus (IOn) was conjunctively applied with AMPA on the vermis. The present data further supports the idea that conjunctive heterosynaptic inputs to cerebellar Purkinje cells can trigger active gene transcription thus possibly contributing to cerebellar long-term plasticity. They also demonstrate that Jun-B may be a useful transcriptional marker to study cerebellar coincidence phenomena.

Afferent Pathways

Evolution of the IL-6/class IB cytokine receptor family in the immune and nervous systems.

It has been suggested that the cytokine receptor has a structure similar to immunoglobulin and this structural similarity has raised the possibility that they have evolved from a common ancestral molecule. In the early 1970s, it was discovered that developing sympathetic neurons could switch from an adrenergic to cholinergic phenotype. The search for a diffusible factor responsible for this eventually led to the identification of leukemia inhibitory factor (LIF). Cholinergic differentiation factor (CDF)/LIF has turned out to belong to the IL-6/class IB cytokine family. In this article we further speculate on a plausible molecular pathway for the IL6/class IB receptor family in the immune and nervous systems. We think that the evolution of the IL-6/class IB receptor family may have occurred in at least two major steps. Firstly, binding subunits of an IL-6 receptor and for a CDF/LIF receptor evolved and secondly, a third binding subunit of a CNTF receptor evolved. Our evolutional consideration predicts that the binding subunits generally determine the specificity of the receptors and it is possible that novel members of the cytokine family and their receptors exist in the nervous system.

Amino Acid Sequence

The conjunctive stimuli that cause long-term desensitization also predominantly induce c-Fos and Jun-B in cerebellar Purkinje cells.

Expression of immediate early genes (IEGs) was examined following long-term desensitization of cerebellar Purkinje cells. This form of desensitization, which may underlie synaptic long-term depression (LTD), was evoked by co-administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and 8-bromo cGMP (8-Br-cGMP). Among the IEGS examined with in situ hybridization and immunohistochemistry, combined application of 8-Br-cGMP and AMPA synergistically enhanced the expression of c-Fos and Jun-B in Purkinje cells. This may suggest a role for active transcriptional complexes such as AP-1 (c-Fos/Jun-B), which could be formed following conjoint inputs to Purkinje cells and which may help to establish cerebellar long-term plasticity.

Animals

Coevolution of cytokine receptor families in the immune and nervous systems.

Close relationships between the nervous system and immune systems at molecular levels have now become evident. Receptors for CDF/LIF and CNTF, i.e., factors which play important roles in the nervous system, share a close structural similarity to those for IL-6, which is a molecule acting in the immune system. Receptors for these three factors belong to a subtype of cytokine receptor family (class IB cytokine receptor). We have constructed a higher subdomain structure of the receptor for CDF/LIF based on its known primary structures. The receptor contains immunoglobulin and fibronectin-like domains, in addition to common domains of the cytokine receptor, similar to those cell surface molecules of the neural immunoglobulin gene super family. These domains appear to have similar structures to the immunoglobulin. These lines of evidence suggest that the class IB cytokine receptor was formed as a result of those fusion of the genes for a more primitive cytokine receptor IA and for the neural immunoglobulin super gene family, and that, likewise, many molecules regulating neural development and those which act in the immune system have a common evolutionary origin.

Amino Acid Sequence

Molecular mechanisms for generation of neural diversity and specificity: roles of polypeptide factors in development of postmitotic neurons.

Development of postmitotic neurons is influenced by two groups of polypeptide factors. Neurotrophic factors promote neuronal survival both in vivo and in vitro. Neuronal differentiation factors influence transmitter phenotypes without affecting neuronal survival. The list of neurotrophic factors is increasing partly because certain growth factors and cytokines have been shown to possess neurotrophic activities and also because new neurotrophic factors including new members of the nerve growth factor (NGF) family have been identified at the molecular level. In vitro assays using recombinant neurotrophic factors and distributions of their mRNAs and proteins have indicated that members of a neurotrophic gene family may play sequential and complementary roles during development and in the adult nervous system. Most of the receptors for neurotrophic factors contain tyrosine kinase domains, suggesting the importance of tyrosine phosphorylation and subsequent signal transduction for their effects. Molecules such as LIF (leukemia inhibitory factor) and CNTF (ciliary neurotrophic factor) have been identified as neuronal differentiation factors in vitro. At the moment, however, it remains to be determined whether or not the receptors for a group of neuronal differentiation factors constitute a gene family or contain domains of kinase or phosphatase activity. Synergetic combinations of neurotrophic and neuronal differentiation factors as well as their receptors may contribute to the generation of neural specificity and diversity.

Animals

Localization of cholinergic differentiation factor/leukemia inhibitory factor mRNA in the rat brain and peripheral tissues.

Sympathetic neurons display considerable plasticity in the neurotransmitter and neuropeptide phenotypes they express in vitro and in vivo. The cholinergic differentiation factor (CDF, also known as leukemia inhibitory factor, LIF) induces cultured rat sympathetic neurons to become cholinergic, without affecting their survival or growth. To understand the role of this factor in normal development, it is essential to determine where it is produced in situ. To localize CDF/LIF mRNA, a semiquantitative, reverse transcription-polymerase chain reaction method was employed. Actin and tubulin mRNA were used as internal controls, and two different sets of CDF/LIF primers were compared. In postnatal rat peripheral tissues, CDF/LIF mRNA was selectively localized in the target area of developing, sympathetic cholinergic neurons; the mRNA was not detected in the targets of sympathetic noradrenergic neurons. This finding supports the hypothesis that CDF/LIF is a target-derived neuronal differentiation factor. In postnatal rat brain, CDF/LIF mRNA is localized selectively in two parts of the visual system, visual cortex and superior colliculus. Thus, CDF/LIF may play a role in this system as well.

Aging

CDF/LIF selectively increases c-fos and jun-B transcripts in sympathetic neurons.

We recently demonstrated that the neuronal cholinergic differentiation factor (CDF) which switches the neurotransmitter phenotype of cultured sympathetic neurons from noradrenergic to cholinergic is identical to leukemia inhibitory factor (LIF). To elucidate some of the initial events leading to the phenotypic switch, the effects of CDF/LIF on the mRNA levels of several immediate early genes were examined in cultured neonatal rat sympathetic neurons. c-fos and jun-B were induced within 30 min of addition of CDF/LIF. In contrast, no effect on the expression of c-myc, fra-1, v-jun or actin mRNA was detected at this time. Thus, CDF/LIF may induce the expression of particular immediate early genes prior to its positive and negative effects on neurotransmitter and neuropeptide gene expression.

Amino Acid Sequence

Relationship between chromosomal breakpoint and molecular rearrangement of T-cell antigen receptors in adult T-cell leukaemia.

The relationship between chromosome breakpoints associated with T-cell antigen receptor (TCR) genes and TCR-alpha/beta/tau/delta rearrangements of peripheral leukaemic cells in 8 Japanese patients with the acute type of adult T-cell leukaemia (ATL) was examined. Break of the 14q11 region with the assigned locus of TCR-alpha/delta was revealed in 6 patients, interstitial deletion of the 7q32-36 region with assigned locus of TCR-beta in 1 patient, and break of the 7p15 region with assigned locus of TCR-tau in 2 patients. Molecular analysis revealed TCR-alpha rearrangement in 7 patients, TCR-beta rearrangement in all patients, and TCR-tau rearrangement in 5 patients. TCR-delta was deleted in all patients. These findings indicate a close relationship between 14q11 anomaly and TCR-alpha rearrangement, which may play an important role in the leukaemogenesis of ATL.

Aged

The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor.

A protein secreted by cultured rat heart cells can direct the choice of neurotransmitter phenotype made by cultured rat sympathetic neurons. Structural analysis and biological assays demonstrated that this protein is identical to a protein that regulates the growth and differentiation of embryonic stem cells and myeloid cells, and that stimulates bone remodeling and acute-phase protein synthesis in hepatocytes. This protein has been termed D factor, DIA, DIF, DRF, HSFIII, and LIF. Thus, this cytokine, like IL-6 and TGF beta, regulates growth and differentiation in the embryo and in the adult in many tissues, now including the nervous system.

Amino Acid Sequence