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.
Neurons, the cells in the brain responsible for carrying information, communicate with each other using a class of chemicals known as neurotransmitters. One family of neurotransmitters, the monoamines, includes dopamine, serotonin, and histamine, all of which play major physiological roles. However, unlike dopamine and serotonin, the regulation of the brain's histamine content is poorly understood. We are using the fruitfly Drosophila melanogaster to study the storage and release of histamine from brain cells. Both mammals and insects use a class of proteins called transporters to store amines, but, to date, amine transporters have been thought to be restricted to neurons. 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. Despite its circumscribed distribution, this protein is required to maintain normal levels of histamine throughout the visual system. We speculate that other animals may use a similar strategy to regulate the function of this important neurotransmitter.