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In the endoplasmic reticulum (ER), disulfide bonds are simultaneously formed in nascent proteins and removed from incorrectly folded or assembled molecules. In this compartment, the redox state must be, therefore, precisely regulated. Here we show that both human Ero1-Lalpha and Ero1-Lbeta (hEROs) facilitate disulfide bond formation in immunoglobulin(More)
Small molecules present during brain tissue homogenization are known to be entrapped within subsequently isolated synaptosomes. We have revisited this technique in view of its systematic utilization to incorporate into nerve endings impermeant probes of large size. Rat neocortical synaptosomes were prepared in the absence or in the presence of each of the(More)
Several genes predisposing to autism spectrum disorders (ASDs) with or without epilepsy have been identified, many of which are implicated in synaptic function. Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. This(More)
Whether exocytosis evoked by a given releasing stimulus from different neuronal families or by different stimuli from one neuronal population occurs through identical mechanisms is unknown. We studied the release of [3H]noradrenaline, [3H]acetylcholine and [3H]dopamine induced by different stimuli from superfused rat brain synaptosomes pretreated with(More)
GABA can evoke norepinephrine (NE) release by activating GABAA receptors or GABA transporters on noradrenergic terminals. The heterocarrier-induced release occurs by conventional exocytosis. We here characterized the mechanism of the GABAA receptor-induced release and investigated what type(s) of voltage-sensitive Ca2+ channels (VSCCs) are involved in the(More)
Release-regulating gamma-aminobutyric acidB (GABAB) autoreceptors were studied in synaptosomes from fresh specimens of human cerebral cortex. The K+ (12 mM)-evoked overflow of [3H]GABA was inhibited by the GABAB receptor agonists (-)-baclofen (EC50 = 1.48 microM) and 3-aminopropylphosphinic acid (3-APPA; EC50 = 0.034 microM). The effect of 10 microM(More)
As previously reported GABAB receptors are heterogeneous. Three pharmacologically distinct receptor subtypes mediating inhibition of gamma-aminobutyric acid (GABA), glutamate or somatostatin release, respectively, exist on axon terminals of rat cerebral cortex. We investigated the novel GABAB receptor antagonist,(More)
Oxidative conditions must be generated in the endoplasmic reticulum (ER) to allow disulfide bond formation in secretory proteins. A family of conserved genes, termed ERO for ER oxidoreductins, plays a key role in this process. We have previously described the human gene ERO1-L, which complements several phenotypic traits of the yeast thermo-sensitive mutant(More)
Many proteins of the secretory pathway contain disulfide bonds that are essential for structure and function. In the endoplasmic reticulum (ER), Ero1 alpha and Ero1 beta oxidize protein disulfide isomerase (PDI), which in turn transfers oxidative equivalents to newly synthesized cargo proteins. However, oxidation must be limited, as some reduced PDI is(More)
Synapsins are synaptic vesicle (SV)-associated phosphoproteins involved in the regulation of neurotransmitter release. Synapsins reversibly tether SVs to the cytoskeleton and their phosphorylation by serine/threonine kinases increases SV availability for exocytosis by impairing their association with SVs and/or actin. We recently showed that synapsin I,(More)