The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse

The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG) analysis of Drosophila mu...

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Main Authors:	Gavin, Brendan A, Arruda, Susan E, Dolph, Patrick J
Format:	Online
Language:	English
Published:	Public Library of Science 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134947/

id	pubmed-2134947
recordtype	oai_dc
spelling	pubmed-21349472007-12-13 The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse Gavin, Brendan A Arruda, Susan E Dolph, Patrick J Research Article The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG) analysis of Drosophila mutants has helped to elucidate some of the genes involved in the visual transduction pathway downstream of the photoreceptor cell, and it is now clear that photoreceptor cell signaling is dependent upon the proper release and recycling of the neurotransmitter histamine. While the neurotransmitter transporters responsible for clearing histamine, and its metabolite carcinine, from the synaptic cleft have remained unknown, a strong candidate for a transporter of either substrate is the uncharacterized inebriated protein. The inebriated gene (ine) encodes a putative neurotransmitter transporter that has been localized to photoreceptor cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in Drosophila. Loss-of-function mutations in ebony, a gene required for the synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG phenotype, while loss-of-function mutations in tan, a gene necessary for the hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine mutants. We also show that by feeding wild-type flies carcinine, we can duplicate components of mutant ine ERGs. Finally, we demonstrate that treatment with H3 receptor agonists or inverse agonists rescue several components of the mutant ine ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence that ine encodes a carcinine neurotransmitter transporter. We also speculate that the oscillations observed in mutant ine ERG traces are the result of the aberrant activity of a putative H3 receptor. Public Library of Science 2007-12 2007-12-07 /pmc/articles/PMC2134947/ /pubmed/18069895 http://dx.doi.org/10.1371/journal.pgen.0030206 Text en © 2007 Gavin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gavin, Brendan A Arruda, Susan E Dolph, Patrick J
spellingShingle	Gavin, Brendan A Arruda, Susan E Dolph, Patrick J The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
author_facet	Gavin, Brendan A Arruda, Susan E Dolph, Patrick J
author_sort	Gavin, Brendan A
title	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
title_short	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
title_full	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
title_fullStr	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
title_full_unstemmed	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse
title_sort	role of carcinine in signaling at the drosophila photoreceptor synapse
description	The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG) analysis of Drosophila mutants has helped to elucidate some of the genes involved in the visual transduction pathway downstream of the photoreceptor cell, and it is now clear that photoreceptor cell signaling is dependent upon the proper release and recycling of the neurotransmitter histamine. While the neurotransmitter transporters responsible for clearing histamine, and its metabolite carcinine, from the synaptic cleft have remained unknown, a strong candidate for a transporter of either substrate is the uncharacterized inebriated protein. The inebriated gene (ine) encodes a putative neurotransmitter transporter that has been localized to photoreceptor cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in Drosophila. Loss-of-function mutations in ebony, a gene required for the synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG phenotype, while loss-of-function mutations in tan, a gene necessary for the hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine mutants. We also show that by feeding wild-type flies carcinine, we can duplicate components of mutant ine ERGs. Finally, we demonstrate that treatment with H3 receptor agonists or inverse agonists rescue several components of the mutant ine ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence that ine encodes a carcinine neurotransmitter transporter. We also speculate that the oscillations observed in mutant ine ERG traces are the result of the aberrant activity of a putative H3 receptor.
publisher	Public Library of Science
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134947/
_version_	1611419191509778432

The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse

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