scholarly journals Motility phenotype in a zebrafish vmat2 mutant

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0259753
Author(s):  
Hildur Sóley Sveinsdóttir ◽  
Amanda Decker ◽  
Christian Christensen ◽  
Pablo Botella Lucena ◽  
Haraldur Þorsteinsson ◽  
...  
Keyword(s):  
Cell Number ◽  
Vesicular Monoamine Transporter ◽  
Monoamine Transporters ◽  
Wild Type ◽  
Behavioural Phenotype ◽  
Vesicular Monoamine Transporter 2 ◽  
Monoamine Transport ◽  
Sleep Parameters ◽  
Solute Carrier ◽  
Dopamine Cell

In the present study, we characterize a novel zebrafish mutant of solute carrier 18A2 (slc18a2), also known as vesicular monoamine transporter 2 (vmat2), that exhibits a behavioural phenotype partially consistent with human Parkinson´s disease. At six days-post-fertilization, behaviour was analysed and demonstrated that vmat2 homozygous mutant larvae, relative to wild types, show changes in motility in a photomotor assay, altered sleep parameters, and reduced dopamine cell number. Following an abrupt lights-off stimulus mutant larvae initiate larger movements but subsequently inhibit them to a lesser extent in comparison to wild-type larvae. Conversely, during a lights-on period, the mutant larvae are hypomotile. Thigmotaxis, a preference to avoid the centre of a behavioural arena, was increased in homozygotes over heterozygotes and wild types, as was daytime sleep ratio. Furthermore, incubating mutant larvae in pramipexole or L-Dopa partially rescued the motor phenotypes, as did injecting glial cell-derived neurotrophic factor (GDNF) into their brains. This novel vmat2 model represents a tool for high throughput pharmaceutical screens for novel therapeutics, in particular those that increase monoamine transport, and for studies of the function of monoamine transporters.

scholarly journals Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters

2020 ◽  
Author(s):  
Carlie A. Hoffman ◽  
Meghan Bucher ◽  
Joshua M. Bradner ◽  
Lauren Jones ◽  
Kenny Igarza ◽  
...  
Keyword(s):  
Real Time ◽  
High Throughput ◽  
Hek293 Cells ◽  
Vesicular Monoamine Transporter ◽  
Environmental Toxicant ◽  
Toxicant Exposure ◽  
Vesicular Monoamine Transporter 2 ◽  
Monoamine Transport ◽  
Plate Assay ◽  
Vesicular Uptake

This manuscript outlines a high-throughput 96-well plate assay to measure the vesicular uptake of the false fluorescent neurotransmitter FFN206 by the vesicular monoamine transporter 2 (VMAT2) in near real-time and following pharmacological and environmental toxicant exposure in HEK293 cells.

scholarly journals Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters

2020 ◽  
Author(s):  
Carlie A. Hoffman ◽  
Meghan Bucher ◽  
Joshua M. Bradner ◽  
Lauren Jones ◽  
Kenny Igarza ◽  
...  
Keyword(s):  
Real Time ◽  
High Throughput ◽  
Hek293 Cells ◽  
Vesicular Monoamine Transporter ◽  
Environmental Toxicant ◽  
Toxicant Exposure ◽  
Vesicular Monoamine Transporter 2 ◽  
Monoamine Transport ◽  
Plate Assay ◽  
Vesicular Uptake

This manuscript outlines a high-throughput 96-well plate assay to measure the vesicular uptake of the false fluorescent neurotransmitter FFN206 by the vesicular monoamine transporter 2 (VMAT2) in near real-time and following pharmacological and environmental toxicant exposure in HEK293 cells.

scholarly journals Putative transmembrane transporter modulates higher-level aggression in Drosophila

2017 ◽  
Vol 114 (9) ◽  
pp. 2373-2378 ◽  
Author(s):  
Budhaditya Chowdhury ◽  
Yick-Bun Chan ◽  
Edward A. Kravitz
Keyword(s):  
Causal Effect ◽  
Nerve Terminals ◽  
Rna Seq ◽  
Wild Type ◽  
Temperature Dependent ◽  
Number Of Genes ◽  
Interesting Family ◽  
Solute Carrier ◽  
Transmembrane Transporter ◽  
Selection Of

By selection of winners of dyadic fights for 35 generations, we have generated a hyperaggressive Bully line of flies that almost always win fights against the parental wild-type Canton-S stock. Maintenance of the Bully phenotype is temperature dependent during development, with the phenotype lost when flies are reared at 19 °C. No similar effect is seen with the parent line. This difference allowed us to carry out RNA-seq experiments and identify a limited number of genes that are differentially expressed by twofold or greater in the Bullies; one of these was a putative transmembrane transporter, CG13646, which showed consistent and reproducible twofold down-regulation in Bullies. We examined the causal effect of this gene on the phenotype with a mutant line for CG13646, and with an RNAi approach. In all cases, reduction in expression of CG13646 by approximately half led to a hyperaggressive phenotype partially resembling that seen in the Bully flies. This gene is a member of a very interesting family of solute carrier proteins (SLCs), some of which have been suggested as being involved in glutamine/glutamate and GABA cycles of metabolism in excitatory and inhibitory nerve terminals in mammalian systems.

scholarly journals Transcriptional activation of vesicular monoamine transporter 2 in the pre-B cell line Ea3.123

1999 ◽  
Vol 337 (2) ◽  
pp. 193 ◽  
Author(s):  
Fiona WATSON ◽  
Damian G. DEAVALL ◽  
Janet A. MACRO ◽  
Rachel KIERNAN ◽  
Rod DIMALINE
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Transcriptional Activation ◽  
Vesicular Monoamine Transporter ◽  
Monoamine Transporter ◽  
Vesicular Monoamine Transporter 2

Platelet Vesicular Monoamine Transporter 2 Density in the Disruptive Behavior Disorders

2011 ◽  
Vol 21 (4) ◽  
pp. 341-344 ◽  
Author(s):  
Gil Zalsman ◽  
Dorit Aslanov-Farbstein ◽  
Moshe Rehavi ◽  
Netta Roz ◽  
Robert Vermeiren ◽  
...  
Keyword(s):  
Disruptive Behavior ◽  
Behavior Disorders ◽  
Disruptive Behavior Disorders ◽  
Vesicular Monoamine Transporter ◽  
Monoamine Transporter ◽  
Vesicular Monoamine Transporter 2

scholarly journals VNUT and VMAT2 segregate within sympathetic varicosities and localize near preferred Cav2 isoforms in the rat tail artery

2019 ◽  
Vol 316 (1) ◽  
pp. H89-H105 ◽  
Author(s):  
Somayeh Mojard Kalkhoran ◽  
Sarah Heather Jane Chow ◽  
Jagdeep Singh Walia ◽  
Cynthia Gershome ◽  
Nickolas Saraev ◽  
...  
Keyword(s):  
Large Fraction ◽  
Atp Release ◽  
Sympathetic Nerves ◽  
Vesicular Monoamine Transporter ◽  
Rat Tail Artery ◽  
Monoamine Transporter ◽  
Vesicular Monoamine Transporter 2 ◽  
Tail Artery ◽  
Vesicle Pools ◽  
Rat Tail

ATP and norepinephrine (NE) are coreleased from peripheral sympathetic nerve terminals. Whether they are stored in the same vesicles has been debated for decades. Preferential dependence of NE or ATP release on Ca2+ influx through specific voltage-gated Ca2+ channel (Cav2) isoforms suggests that NE and ATP are stored in separate vesicle pools, but simultaneous imaging of NE and ATP containing vesicles within single varicosities has not been reported. We conducted an immunohistochemical study of vesicular monoamine transporter 2 (VMAT2/SLC18A2) and vesicular nucleotide translocase (VNUT/SLC17A9) as markers of vesicles containing NE and ATP in sympathetic nerves of the rat tail artery. A large fraction of varicosities exhibited neighboring, rather than overlapping, VNUT and VMAT2 fluorescent puncta. VMAT2, but not VNUT, colocalized with synaptotagmin 1. Cav2.1, Cav2.2, and Cav2.3 are expressed in nerves in the tunica adventitia. VMAT2 preferentially localized adjacent to Cav2.2 and Cav2.3 rather than Cav2.1. VNUT preferentially localized adjacent to Cav2.3 > Cav2.2 >> Cav2.1. With the use of wire myography, inhibition of field-stimulated vasoconstriction with the Cav2.3 blocker SNX-482 (0.25 µM) mimicked the effects of the P2X inhibitor suramin (100 µM) rather than the α-adrenergic inhibitor phentolamine (10 µM). Variable sensitivity to SNX-482 and suramin between animals closely correlated with Cav2.3 staining. We concluded that a majority of ATP and NE stores localize to separate vesicle pools that use different synaptotagmin isoforms and that localize near different Cav2 isoforms to mediate vesicle release. Cav2.3 appears to play a previously unrecognized role in mediating ATP release in the rat tail artery. NEW & NOTEWORTHY Immunofluorescence imaging of vesicular nucleotide translocase and vesicular monoamine transporter 2 in rat tail arteries revealed that ATP and norepinephrine, classical cotransmitters, localize to well-segregated vesicle pools. Furthermore, vesicular nucleotide translocase and vesicular monoamine transporter 2 exhibit preferential localization with specific Cav2 isoforms. These novel observations address long-standing debates regarding the mechanism(s) of sympathetic neurotransmitter corelease.

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