Zhao-Wen Wang et al. (2001) International C. elegans Meeting "SLO-1 Potassium Channel Regulates Duration of Neurotransmitter Release"

Zhao-Wen Wang, Lawrence Salkoff, Owais Saifee, Michael L Nonet

[International C. elegans Meeting, 2001]

In order to identify negative regulators of synaptic transmission, we screened the entire genome of C. elegans for suppressors of unc-64(e246) , a hypomorphic syntaxin allele that greatly depresses synaptic function. Among 10 suppressors examined, six were alleles of the Ca 2+ -activated K + channel (SLO-1), notably, the only K + channel gene identified. unc-64 animals were lethargic and resistant to treatment with the cholinesterase inhibitor aldicarb. slo-1 mutations partially suppressed the lethargy and aldicarb-resistance of unc-64 . Expression of wild-type SLO-1 in neurons, but not muscle, reversed the suppression. To investigate the physiological basis of suppression, we examined evoked excitatory postsynaptic currents (EPSCs) and spontaneous miniature postsynaptic currents (MPSCs) at the neuromuscular junction under voltage-clamp (-60 mV) conditions. The EPSC was induced by stimulating the ventral nerve cord with a 0.5-ms DC pulse. Evoked EPSCs at the unc-64 neuromuscular junction were small, with an amplitude of ~15% and quantal content of ~5% of wild-type. Addition of a slo-1 mutation prolonged EPSC duration, resulting in a 4-fold increase in quantal content. slo-1 mutations also prolonged EPSCs and increased their amplitudes in the absence of unc-64 . In contrast, MPSC frequency and amplitude were not altered by slo-1 mutations, suggesting that the effects of the mutations were presynaptic. These results suggest that BK channels plays a key role in synaptic transmission, possibly by terminating Ca 2+ influx into the presynaptic nerve terminal.

Zhao-Wen Wang et al. (2003) International Worm Meeting "Presynaptic Ryanodine Receptors Mediate Spontaneous Neurotransmitter Release at the C. elegans Neuromuscular Junction"

Lawrence Salkoff, Ding-Xia Shen, Zhao-Wen Wang, Michael L Nonet

[International Worm Meeting, 2003]

Spontaneous miniature postsynaptic potentials or currents (minis) are generally considered fusion events of individual synaptic vesicles. Consistent with this notion, minis at vertebrate neuromuscular junctions (NMJs) often appear unitary, and show a normal distribution in amplitude histograms. However, at many other synapses, such as synapses in the vertebrate central nervous system, amplitude histograms of minis are positively skewed due to the presence of numerous large-amplitude events. Little is known about the origin of large-amplitude spontaneous events. At the C. elegans NMJ, amplitudes of minis vary greatly. Although their average amplitude is about 25 pA, many are over 50 pA. We investigated the mechanism of large-amplitude minis at the C. elegans NMJ. Minis were recorded from body-wall muscle cells voltage-clamped at -60 mV. Large-amplitude minis persisted in the absence of external Ca2+, suggesting that they are not endogenous evoked responses. Experiments with nicotinic and GABAergic receptor blockers, and with mutants of GABAergic receptors (unc-49) suggest that large-amplitude minis are of both cholinergic and GABAergic origins. Large-amplitude minis were absent in unc-68(r1162), a null mutant of the ryanodine receptor (RyR). Inclusion of a RyR blocker in the recording pipette to selectively block postsynaptic RyRs had no effect on minis, whereas application of a membrane permeant RyR blocker to the NMJ preparation, which blocked both presynaptic and postsynaptic RyRs, produced effects similar to that of the unc-68 mutant, suggesting that large-amplitude minis are mediated by presynaptic RyRs. The frequency of minis was also severely reduced in the RyR mutant and in wild-type animals treated with a RyR blocker. The effect of RyRs appeared specific because large-amplitude minis remained in other mutants affecting intracellular Ca2+ mobilization (itr-1 and crt-1), or release of large dense core vesicles (unc-31). In the presence of extracellular Ca2+ (1-5 mM), mini frequency was high (~40 Hz). Elimination of external Ca2+ reduced mini frequency by ~80%. Preliminary results suggest that the effect of external Ca2+ on minis is mediated at least in part by presynaptic RyRs, perhaps through a process known as Ca2+-induced Ca2+ release.

Infarinato N (2019) J Cell Biol "Xiaochen Wang: Building up our understanding of breaking down."

Infarinato N

[J Cell Biol, 2019]

Wang studies lysosomal degradation pathways using <i>C. elegans</i> as a model system.

Wang JT et al. (2014) Curr Biol "P granules."

Seydoux G, Wang JT

[Curr Biol, 2014]

Wang and Seydoux discuss the functional importance of P granules - the germline-specific RNA granules of C. elegans.

Goulding M (2012) Neuron "Motor neurons that multitask."

Goulding M

[Neuron, 2012]

Animals use a form of sensory feedback termed proprioception to monitor their body position and modify the motor programs that control movement. In this issue of Neuron, Wen etal. (2012) provide evidence that a subset of motor neurons function as proprioceptors in C.elegans, where B-type motor neurons sense body curvature to control the bending movements that drive forward locomotion.

Munro E (2017) Dev Cell "Protein Clustering Shapes Polarity Protein Gradients."

Munro E

[Dev Cell, 2017]

In this issue of Developmental Cell, Dickinson etal. (2017) and Rodriguez etal. (2017), along with Wang etal. (2017) in Nature Cell Biology, show how PAR protein oligomerization can dynamically couple protein diffusion and transport by cortical flow to control kinase activity gradients and polarity in the C.elegans zygote.

Rashid S et al. (2017) Dev Cell "Packing on the Pounds in Response to Bacterial Growth Conditions."

Rashid S, MacNeil LT

[Dev Cell, 2017]

Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C.elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.

Vincenz L et al. (2014) Cell "Sugarcoating ER Stress."

Vincenz L, Hartl FU

[Cell, 2014]

The hexosamine biosynthetic pathway (HBP) generates metabolites for protein N- and O-glycosylation. Wang et al. and Denzel et al. report a hitherto unknown link between the HBP and stress in the endoplasmic reticulum. These studies establish the HBP as a critical component of the cellular machinery of protein homeostasis.

Sural S (2023) Trends Genet "Protecting axons in grandchildren."

Sural S

[Trends Genet, 2023]

Prenatal exposure to environmental agents can influence the fitness of not only the fetus, but also subsequent generations. In a recent study, Wang et al. demonstrated that feeding ursolic acid (UA), a plant-derived compound, to Caenorhabditis elegans mothers during their reproductive period prevented neurodegeneration in not only their offspring, but also the F2 progeny.

Spalthoff C et al. (2016) Neuron "Sensing pH with TMCs."

Gopfert MC, Spalthoff C

[Neuron, 2016]

Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C.elegans. In this issue of Neuron, Wang etal. (2016) report that C.elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive.