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Biomedical subjects

J H Chou

Publications and source records attributed to J H Chou.

14 recordsLinked to original sources
PubMed2001

The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction.

Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

Alternative Splicing↗
PubMed2000

Binding of Rab3A to synaptic vesicles.

Prenylated Rab GTPases cycle between membrane-bound and soluble forms. Membrane-bound GDP-Rabs interact with GDP dissociation inhibitor (GDI), resulting in the dissociation of a Rab.GDI complex, which in turn serves as a precursor for the membrane re-association of Rabs. We have now characterized the binding of Rab3A to synaptic vesicles in vitro using either purified complexes or rat brain cytosol as source for GDI.Rab3A. Binding of Rab3A results in the immediate release of GDI from the membrane. Furthermore, binding does not require the presence of additional guanine nucleotides (GDP or GTP) or of cytosolic factors. Although nucleotide exchange follows binding, binding is initially reversible, suggesting that binding of GDP-Rab3A and nucleotide exchange are separate and independent events. Comparison with the binding of Rab1B revealed that both Rab proteins bind preferentially to their respective resident membranes although some promiscuity was observable. Binding is saturable and involves a protease-sensitive binding site that is tightly associated with the vesicle membrane.

Animals↗
PubMed1997

The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells.

The nematode Caenorhabditis elegans exhibits behavioral responses to many volatile odorants. Chemotaxis toward one such odorant, diacetyl (butanedione), requires the function of a seven-transmembrane receptor protein encoded by the odr-10 gene. To determine directly whether ODR-10 protein is an odorant receptor, it is necessary to express the protein in a heterologous system and show that it responds to diacetyl by activation of a G protein signaling pathway. Here we demonstrate that human cells expressing ODR-10 on their surfaces exhibit a transient elevation in intracellular Ca2+ levels after diacetyl application. Volatile compounds that differ from diacetyl only by the addition of a methyl group (2,3-pentanedione) or the absence of a keto group (butanone) are not ODR-10 agonists. Behavioral responses to these compounds are not dependent on odr-10 function, so ODR-10 specificity in human cells resembles in vivo specificity. The apparent affinity of ODR-10 for diacetyl observed in human cells is consistent with the diacetyl concentration ranges that allow efficient nematode chemotaxis. ODR-10 expressed in human cells also responds to two anionic compounds, pyruvate and citrate, which are metabolic precursors used for diacetyl production by certain bacterial species. Ca2+ elevation in response to ODR-10 activation is due to release from intracellular stores.

Animals↗
PubMed1996

Rab3 reversibly recruits rabphilin to synaptic vesicles by a mechanism analogous to raf recruitment by ras.

GTP activates the interaction between the synaptic vesicle proteins rabphilin and rab3. This raises the question of whether rabphilin is a resident vesicle protein that recruits rab3 in a stage-dependent fashion, or if it is instead an effector protein recruited by rab3. We now show that rabphilin, like rab3, dissociates from synaptic vesicles after exocytosis in a manner requiring both Ca2+ and membrane fusion. Rabphilin interacts with GTP-rab3 via a N-terminal domain comprising a novel Zn2+(-)finger motif, and this interaction is essential for rabphilin binding to synaptic vesicles. Thus, in the same way that ras recruits raf to the plasma membrane, rab3 reversibly recruits rabphilin to synaptic vesicles in a stage-dependent manner. These results reveal an unexpected similarity between the molecular mechanisms by which small G protein function in recruiting effector proteins to membranes during membrane traffic and signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1996

odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl.

Olfactory signaling is initiated by interactions between odorants and olfactory receptors. We show that the C. elegans odr-10 gene is likely to encode a receptor for the odorant diacetyl. odr-10 mutants have a specific defect in chemotaxis to diacetyl, one of several odorants detected by the AWA olfactory neurons. odr-10 encodes a predicted seven transmembrane domain receptor; a green fluorescent protein-tagged Odr-10 protein is localized to the AWA sensory cilia. odr-10 expression is regulated by odr-7, a transcription factor implicated in AWA sensory specification. Expression of odr-10 from a heterologous promoter directs behavioral responses to diacetyl, but not to another odorant detected by the AWA neurons. These results provide functional evidence for a specific interaction between an olfactory receptor protein and its odorant ligand.

Amino Acid Sequence↗
PubMed1995

Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans.

Using their senses of taste and smell, animals recognize a wide variety of chemicals. The nematode C. elegans has only fourteen types of chemosensory neurons, but it responds to dozens of chemicals, because each chemosensory neuron detects several stimuli. Here we describe over 40 highly divergent members of the G protein-coupled receptor family that could contribute to this functional diversity. Most of these candidate receptor genes are in clusters of two to nine similar genes. Eleven of fourteen tested genes appear to be expressed in small subsets of chemosensory neurons. A single type of chemosensory neuron can potentially express at least four different receptor genes. Some of these genes might encode receptors for water-soluble attractants, repellents, and pheromones.

1-Octanol↗
PubMed1993

Posttranscriptional repression of Escherichia coli OmpF protein in response to redox stress: positive control of the micF antisense RNA by the soxRS locus.

The soxRS regulon is a cornerstone of the adaptive defense systems of Escherichia coli against oxidative stress. Unexpectedly, activation of this regulon also enhances bacterial resistance to multiple antibiotics that seem unrelated to oxygen radicals. We previously correlated this multiple antibiotic resistance with a reduced rate of synthesis of the OmpF outer membrane porin that does not affect the OmpC or OmpA porins. Studies presented here, with operon and gene fusions of ompF to lacZ, show that the soxRS-dependent repression of OmpF is achieved posttranscriptionally. We also show posttranscriptional repression of OmpF mediated by the soxQ1 mutation, which maps to the marA locus. These repressions are dependent on the micF gene, which encodes a small RNA partially complementary to the 5' end of the ompF message. Northern (RNA) blotting experiments show that micF transcription is strongly inducible by the superoxide-generating agent paraquat in a manner that depends completely on the soxRS locus. The soxR-constitutive and soxQ1 mutations elevate the expression of micF in the absence of redox stress. However, the antibiotic resistance mediated by a soxR-constitutive mutation was only partially reversed upon deletion of micF. The soxRS regulon therefore includes other components that contribute to general antibiotic resistance, although the relation of this phenotype to oxidative stress remains to be established.

Bacterial Outer Membrane Proteins↗
PubMed1992

Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis.

Tetanus toxin is a potent neurotoxin that inhibits the release of neurotransmitters from presynaptic nerve endings. The mature toxin is composed of a heavy and a light chain that are linked via a disulfide bridge. After entry of tetanus toxin into the cytoplasm, the released light chain causes block of neurotransmitter release. Recent evidence suggests that the L-chain may act as a metalloendoprotease. Here we demonstrate that blockade of neurotransmission by tetanus toxin in isolated nerve terminals is associated with a selective proteolysis of synaptobrevin, an integral membrane protein of synaptic vesicles. No other proteins appear to be affected by tetanus toxin. In addition, recombinant light chain selectively cleaves synaptobrevin when incubated with purified synaptic vesicles. Our data suggest that cleavage of synaptobrevin is the molecular mechanism of tetanus toxin action.

Animals↗
PubMed1991

Activation of oxidative stress genes by mutations at the soxQ/cfxB/marA locus of Escherichia coli.

Exposure of Escherichia coli to superoxide-generating drugs, such as menadione or paraquat, uniquely induces approximately 40 proteins, nine of which are under the positive control of the soxR locus (at min 92). We report here that certain mutations at a separate locus that we have named soxQ (at min 34) confer some of the phenotypes seen in soxR-constitutive strains, including resistance to menadione. A previously known mutation called cfxB, identified through antibiotic resistance, is likely an allele of soxQ. The soxQ1 and cfxB mutations cause transcriptional activation of the genes that encode Mn-containing superoxide dismutase, glucose 6-phosphate dehydrogenase, and the soi-17/19::lac and soi-28::lac fusions. These genes are also activated by soxR, but the soxQ1 and cfxB mutations increase the synthesis of seven other proteins not influenced by soxR. Moreover, the soxQ1- and cfxB-dependent phenotypes do not depend on the soxR gene, and gene induction by soxR in response to redox stress does not depend on the soxQ locus. As well as increasing cellular resistance to some oxidants, the soxQ1 and cfxB mutations confer elevated resistance to various antibiotics, probably via diminished expression of outer membrane protein OmpF. The marA1 multiple-antibiotic resistance mutation (also at min 34) behaves like a weak allele of soxQ but probably resides in a nearby gene that, with soxQ, is part of a regulatory complex. We propose that soxQ helps control some oxidative stress proteins as part of another regulon that responds to an unknown environmental signal.

Anti-Bacterial Agents↗
PubMed1990

Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli.

Escherichia coli responds to superoxide-generating agents by inducing approximately 40 proteins. We have identified a genetic locus, soxR (superoxide response), that positively regulates 9 of these proteins during superoxide stress. Induction under soxR control is at the transcriptional level, as shown with lac fusions to five paraquat-inducible promoters. Members of the soxR regulon include at least three proteins with demonstrable antioxidant roles: Mn-containing superoxide dismutase (which destroys superoxide radicals), endonuclease IV (which repairs radical-induced damages in DNA), and glucose-6-phosphate dehydrogenase (which produces NADPH). Induction of the soxR regulon also leads to diminished levels of the major outer membrane protein OmpF and alteration of the small-subunit ribosomal protein S6. These latter changes confer resistance to a variety of antibiotics. The soxR regulon may thus operate as an inducible defense against xenobiotics in general.

Anti-Bacterial Agents↗
PubMed1990

Outbreak of type A botulism caused by a commercial food product in Taiwan: clinical and epidemiological investigations.

In late September 1986, we found 7 patients from a printing factory in Chang-Hwa city who developed an endemic disease manifested by general malaise, ptosis, double vision, dysarthria, dysphagia, and proximal limb weakness. After clinical, epidemiological, microbiological, and toxicological investigations, an outbreak of botulism was confirmed 2 weeks later, Commercially canned peanuts made by an unlicensed cannery were identified as the vehicle of botulinum toxin transmission. Antitoxin was given to 2 patients who needed ventilator support. One of the 7 victims died from medical complications and the remaining 6 patients recovered. Several administrative problems exposed in this outbreak were the poor governmental supervision of canned food, the inadequate quantities of "orphan drugs" stored in this country, the inefficient system for recalling the problem products, and the delayed broadcasting of warnings to the public. Since commercially processed food is increasingly popular with modernization, the possibility of future botulism outbreaks should not be overlooked.

Adolescent↗
PubMed1988

An outbreak of type A foodborne botulism in Taiwan due to commercially preserved peanuts.

Until recently, botulism was not recognized as an important public health problem in Taiwan. In 1986, an outbreak of type A foodborne botulism resulted in nine cases, two of them fatal. The vehicle in this outbreak was commercially preserved peanuts processed by an improperly equipped, unlicensed cannery. A single batch of peanuts was implicated; however, we could not determine why this particular batch was contaminated. Efforts to recall the product were hampered by a lack of distribution records. Mass media announcements were used to warn the public about the outbreak, and preliminary data suggest the ensuing publicity improved botulism surveillance. The local preference for low-acid preserved foods, increasing consumerism, the shortage of adequately trained inspectors are factors which probably contributed to this outbreak. Stricter enforcement of food sanitation policies are needed to meet the changing situation in Taiwan.

Adult↗