2/28/2023 0 Comments 2110 adobe drive il![]() ![]() In the mature mammalian CNS, VGLUT1 and VGLUT2 appear in essentially nonoverlapping distributions, although they are coexpressed in some neurons during development ( Fremeau et al., 2004a). Vertebrates possess three VGLUT isoforms. Furthermore, mRNA for VGLUT1 has been isolated from cochlear hair cells, and at least one group has reported VGLUT1 protein at the guinea pig afferent synapse ( Furness and Lawton, 2003). ![]() It was reported previously that vesicular glutamate transporter 3 (VGLUT3) immunoreactivity is present in the sensory epithelial cells and afferent fibers of the peripheral vestibular system in rats ( Wang et al., 2007). EPSCs in afferent boutons are mediated by AMPA receptors ( Glowatzki and Fuchs, 2002), supporting cells abutting the afferent synapse express the glutamate-aspartate transporter (GLAST) ( Furness et al., 2002), and phosphate-activated glutaminase (a glutamate synthetic enzyme) has been detected in the mitochondria of hair cells in the mammalian cochlea ( Takumi et al., 1999). Several lines of evidence indicate that the hair-cell afferent synapse is glutamatergic. How this enormous pool of SVs is generated, tethered, and regulated is unknown. It is estimated that frog saccular hair cells contain up to 200,000–600,000 clear core SVs ( Lenzi et al., 1999). Synaptic ribbons confer remarkable release properties to the hair-cell afferent synapse: exocytosis (and subsequent replenishment) at a single synapse can occur at rates approaching 1000 SV/s ( Moser and Beutner, 2000 Griesinger et al., 2005), and unlike conventional synapses, tens of thousands of SVs can be released from hair cells in response to strong stimulation ( Schnee et al., 2005). They possess a highly specialized structure, the synaptic ribbon, which coordinates synaptic vesicles (SVs) at the active zone. Hair cells are the sensory receptors for the auditory and vestibular system. Lack of postsynaptic action currents in the mutants suggests that the remaining hair-cell synaptic vesicles contain insufficient levels of glutamate for generation of action potentials in first-order neurons. At the ultrastructural level, mutant asteroid/vglut3 hair cells show a decrease in the number of ribbon-associated synaptic vesicles, indicating a role for Vglut3 in synaptic vesicle biogenesis and/or tethering to the ribbon body. In support of this notion, action currents in postsynaptic acousticolateralis neurons are absent in asteroid/vglut3 mutants. Based on the localization of Vglut3 in hair cells, we suspected that the lack of vestibulo-ocular and acoustic startle reflexes in asteroid/vglut3 mutants was attributable to a defect in synaptic transmission in hair cells. Antibodies against Vglut3 label the basal end of hair cells and labeling is not present in asteroid/vglut3 mutants. A second transporter gene, vglut1, is also expressed in zebrafish hair cells, but the level of vglut1 mRNA is not increased in the absence of Vglut3. In situ hybridization shows that vglut3 is exclusively expressed in hair cells of the ear and lateral line organ. A splice site mutation in exon 2 of vglut3 results in a severe truncation of the predicted protein product and morpholinos directed against the vglut3 ATG start site or the affected splice junction replicate the asteroid phenotype. Here we report that asteroid, a gene identified in an ethylnitrosourea mutagenesis screen of zebrafish larvae for auditory/vestibular mutants, encodes vesicular glutamate transporter 3 (Vglut3). ![]() Sécuriser votre OT et IoT Fournissez une connectivité Zero Trust pour les appareils OT et IoT et un accès distant sécurisé aux systèmes OT.Hair cells detect sound and movement and transmit this information via specialized ribbon synapses. Sécuriser vos charges de travail Créez et exécutez des applications cloud sécurisées, activez la connectivité cloud Zero Trust et protégez les charges de travail du data center au cloud. Sécuriser vos utilisateurs Offrez aux utilisateurs un accès transparent, sécurisé et fiable aux applications et aux données. ![]()
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