A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

Rafael Romero-Calderón,Nigel T Maidment,Anne F Simon,Anna Grygoruk,David E Krantz,Jolanta Borycz,Ian A Meinertzhagen,Susan K Yee,Larry C Ackerson,Bernhard T Hovemann,Guido Uhlenbrock,Amy Shyer,Patrick J Dolph

doi:10.1371/journal.pgen.1000245

Rafael Romero-Calderón, Nigel T Maidment + Show 11 more

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https://doi.org/10.1371/journal.pgen.1000245

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Abstract

Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

Highlights

Histamine was first identified as a potential neuromodulator at the turn of the last century, and is known to regulate multiple physiological processes in mammals as well as invertebrates [1,2,3,4,5,6,7,8,9]
We have found that the support cells, or glia, that facilitate the function of neurons in the fly’s visual system contain a new form of monoamine transporter
We show here that DVMAT-B is not expressed in neurons, but rather in a subset of glia that are adjacent to the retina and store histamine

Summary

Introduction

Histamine was first identified as a potential neuromodulator at the turn of the last century, and is known to regulate multiple physiological processes in mammals as well as invertebrates [1,2,3,4,5,6,7,8,9]. For all other classical neurotransmitters, the transport proteins responsible for neurotransmitter storage and recycling play a critical role in regulating the amount of transmitter that is available for signaling at the synapse [10,11]. To understand the mechanisms by which histaminergic signaling is regulated, it will be critical to determine the transporters and transport mechanisms by which histamine and its metabolites are stored, released and recycled. Both cell surface and vesicular transporters are required for neurotransmitter release and recycling. All classical neurotransmitters are synthesized in the cytoplasm and must undergo transport into the lumen of secretory vesicles for regulated release. Histamine is transported into synaptic vesicles and secretory granules by the neuronal isoform of VMAT, VMAT2 [15,16,17,18]

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