Rohon-Beard (RB) spinal neurons of Xenopus larvae are depolarized by GABA. To study the mechanisms underlying this distinctive response, intracellular and patch-clamp recordings were made from RB in situ. The intracellularly recorded GABA reversal potential (EREV) was near -30 mV normal saline approximately 25 more negative Na(+)-free saline. Whole-cell neighboring dorsolateral interneurons (DLi) revealed that responses both cells mediated GABAA receptors. Currents elicited mimicked muscimol...

A Drosophila forward genetic screen for mutants with defective synaptic development identified bad reception ( brec ). Homozygous are embryonic lethal, paralyzed, and show no detectable transmission at the glutamatergic neuromuscular junction (NMJ). Genetic mapping, complementation tests, genomic sequencing that mutations disrupt a previously uncharacterized ionotropic glutamate receptor subunit, named here “GluRIID.” GluRIID is expressed in postsynaptic domain of NMJ, as well widely...

<i>Volado</i>, the gene encoding <i>Drosophila</i>αPS3-integrin, is required for normal short-term memory formation (Grotewiel et al., 1998), supporting a role integrins in synaptic modulation mechanisms. We show that Volado protein (VOL) localized to central and peripheral larval <i>Drosophila</i>synapses. VOL strongly concentrated subpopulation of boutons CNS neuropil variable subset at neuromuscular junctions (NMJs). Mutant morphological functional phenotypes were analyzed...

We report functional neuronal and synaptic transmission properties in DrosophilaCNS neurons. Whole cell current- voltage-clamp recordings were made from dorsally positioned neurons the larval ventral nerve cord. Comparison of Green Fluorescent Protein markers intracellular dye labeling revealed that recorded cells consisted primarily identified motor Neurons had resting potentials −50 to −60 mV fired repetitive action (APs) response depolarizing current injection. Acetylcholine application...

A screen for Drosophila synaptic dysfunction mutants identified slug-a-bed ( slab ). The gene encodes ceramidase, a central enzyme in sphingolipid metabolism and regulation. Sphingolipids are major constituents of lipid rafts, membrane domains with roles vesicle trafficking, signaling pathways. Null arrest as fully developed embryos severely reduced movement. SLAB protein is widely expressed different tissues but enriched neurons at all stages development. Targeted neuronal expression...

Bidirectional trans-synaptic signals induce synaptogenesis and regulate subsequent synaptic maturation. Presynaptically secreted Mind the gap (Mtg) molds cleft extracellular matrix, leading us to hypothesize that Mtg functions generate intercellular environment required for efficient signaling. We show in Drosophila Jelly belly (Jeb) its receptor tyrosine kinase Anaplastic lymphoma (Alk) are localized developing synapses. Jeb localizes punctate aggregates central neuropil neuromuscular...

A family of three position-specific (PS) integrins are expressed at the Drosophila neuromuscular junction (NMJ): a beta subunit ((betaPS), in both presynaptic and postsynaptic membranes, two alpha subunits (alphaPS1, alphaPS2), least membrane. PS appear postembryonic NMJs coincident with onset rapid morphological growth terminal type-specific differentiation, restricted to type I synaptic boutons, which mediate fast, excitatory glutamatergic transmission. We show that distinctive hypomorphic...

A systematic Drosophila forward genetic screen for photoreceptor synaptic transmission mutants identified no-on-and-no-off transient C (nonC) based on loss of retinal responses to light stimulation. The cloned gene encodes phosphatidylinositol-3-kinase-like kinase (PIKK) Smg1, a regulatory the nonsense-mediated decay (NMD) pathway. Smg proteins act in an mRNA quality control surveillance mechanism selectively degrade transcripts containing premature stop codons, thereby preventing...

Formation and regulation of excitatory glutamatergic synapses is essential for shaping neural circuits throughout development. In a Drosophila genetic screen synaptogenesis mutants, we identified mind the gap ( mtg ), which encodes secreted, extracellular N-glycosaminoglycan-binding protein. MTG expressed neuronally detected in synaptic cleft, required to form specialized transsynaptic matrix that links presynaptic active zone with post-synaptic glutamate receptor (GluR) domain. Null...

In Drosophila, the secreted signaling molecule Jelly Belly (Jeb) activates anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase, in multiple developmental and adult contexts. We have shown previously that Jeb Alk are highly enriched at Drosophila synapses within CNS neuropil neuromuscular junction (NMJ) postulated conserved intercellular function. At embryonic larval NMJ, is localized motor neuron presynaptic terminal whereas concentrated muscle postsynaptic domain surrounding...

The ClC-3 2Cl

Key points LRRC8A‐containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production tumour necrosis factor‐α (TNFα) signalling. Here we show that LRRC8C 8D also co‐immunoprecipitate Nox1 in vascular smooth muscle cells. knockdown inhibited TNFα‐induced O 2 •− production, receptor endocytosis, nuclear factor‐κB (NF‐κB) activation proliferation while LRRC8D enhanced NF‐κB activation. Significant changes LRRC8 isoform expression human atherosclerosis psoriasis...

Abstract Mind‐the‐Gap (MTG) is required during synaptogenesis of the Drosophila glutamatergic neuromuscular junction (NMJ) to organize postsynaptic domain. Here, we generate MTG::GFP transgenic animals demonstrate MTG synaptically targeted, secreted, and localized punctate domains in synaptic extracellular matrix (ECM). NMJs form specialized ECM carbohydrate domains, with moieties integrin receptors occupying overlapping territories. Presynaptically secreted recruits reorganizes...

At many mature vertebrate glutamatergic synapses, excitatory transmission strength and plasticity are regulated by AMPA NMDA receptor (AMPA-R NMDA-R) activation patterns of presynaptic transmitter release. Both receptors potentially direct neuronal differentiation mediating postsynaptic Ca(2+) influx during early development. However, the development synaptic expression colocalization has been examined developmentally in only a few systems, changes release properties at synapses have not...

Abstract Leucine‐rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro‐contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II stretch. LRRC8A associates with NADPH oxidase 1 (Nox1) supports extracellular superoxide production. We tested the hypothesis that VRACs modulate TNFα signaling vasomotor function in mice lacking exclusively vascular smooth muscle cells (VSMCs, Sm22α‐Cre, Knockout). Knockout (KO)...

1. Developmental changes in single acetylcholine (ACh) receptor channel properties were analysed cultured Xenopus myocytes at low temperatures (11‐16 degrees C) using the cell‐attached patch clamp technique. Single‐channel recordings done fourteen stages of development ranging from several hours (stage 21) to 5 days 47) after ACh receptors first appear muscle membrane. 2. Two types channels, conductance and high conductance, which have been described previously, observed all stages. At...

Mind-the-Gap (MTG) is required for neuronal induction of Drosophila neuromuscular junction (NMJ) postsynaptic domains, including glutamate receptor (GluR) localization. We have previously hypothesized that MTG secreted from the presynaptic terminal to reside in synaptic cleft, where it binds glycans organize heavily glycosylated, extracellular synaptomatrix transsynaptic signaling between neuron and muscle. In this study, we test hypothesis with structure-function analyses predicted signal...

1. Single acetylcholine (ACh) receptor channel currents were analysed in Xenopus myocyte culture. Channel events activated by ACh recorded using the cell‐attached patch clamp technique at low temperatures (11.2‐15.8 degrees C) and 100 mV hyperpolarization over average resting membrane potential of ‐75 mV. There two types channels, low‐ high‐conductance as reported previously, with unitary current amplitudes 4.7 +/‐ 0.4 pA (mean S.D., n = 17) 6.6 1.2 (n 14), respectively. 2. At concentrations...