A Glial Variant of the Vesicular Monoamine Transporter Is Required To Store Histamine in the Drosophila Visual System

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.

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin inDrosophila melanogaster

“…For all other experiments WT controls were Canton-S (CS). The dVMAT null, homozygous for the loss-of-function allele (dVMAT P1 ), and the UAS-DVMAT transgene have been previously described (Oh et al 2003;Chang et al 2006;Romero-Calderon et al 2008;Simon et al 2009). Note that the UAS-DVMAT transgene used here encodes the neuronal isoform of DVMAT (DVMAT-A); a distinct RNA splice variant of dVMAT (DVMAT-B) is expressed only in a small subset of glia in the visual system and is unlikely to be relevant to the behaviors discussed here (Greer et al 2005;Romero-Calderon et al 2008).…”

“…The dVMAT null, homozygous for the loss-of-function allele (dVMAT P1 ), and the UAS-DVMAT transgene have been previously described (Oh et al 2003;Chang et al 2006;Romero-Calderon et al 2008;Simon et al 2009). Note that the UAS-DVMAT transgene used here encodes the neuronal isoform of DVMAT (DVMAT-A); a distinct RNA splice variant of dVMAT (DVMAT-B) is expressed only in a small subset of glia in the visual system and is unlikely to be relevant to the behaviors discussed here (Greer et al 2005;Romero-Calderon et al 2008). Gal4 driver lines include those previously shown to drive expression in serotonergic (TrH-Gal4) (Park et al 2006), dopaminergic (TH-Gal4) , tyraminergic and octopaminergic (Tdc2-Gal4) (Cole et al 2005), and both serotonergic and dopaminergic (Ddc-Gal4) (Li et al 2000) neurons.…”

The metabolism of histamine in theDrosophilaoptic lobe involves an ommatidial pathway: β-alanine recycles through the retina

“…To generate antibody against VMAT-B, a peptide representing the last 21 amino acids of DVMAT-B (SVPDSDAEAGRTNEAYESERL, B1-peptide) was synthesized, HPLC purified, conjugated to KLH and then injected into rats (Romero-Calderón et al, 2008). Its specificity has been confirmed by reduced immunolabelling in the 14 excision allele of dVMAT (Romero-Calderón et al, 2008). Mouse monoclonal antibody 40-1a (Developmental Studies Hybridoma Bank, Iowa City, IA, USA) was raised against -gal and labels lacZ-expressing Drosophila cells, but not brains lacking UAS-lacZ.…”

Drosophila Vesicular Monoamine Transporter Mutants Can Adapt to Reduced or Eliminated Vesicular Stores of Dopamine and Serotonin

“…We have shown previously that the dVMAT gene contains two splice variants, dVMAT-A and -B and that overexpression of DVMAT-A protein has a dramatic effect on amine-dependent behaviors (Greer et al 2005;Chang et al 2006). More recently, we have characterized mutations in the dVMAT gene, but limited our phenotypic characterization to the function of DVMAT-B, an isoform found exclusively in a small subset of glia in the visual system (Romero-Calderó n et al 2008). Here, we present a more in-depth characterization of the dVMAT loss-of-function alleles, focusing on the function of DVMAT-A, which is expressed in all dopaminergic, serotonergic, and octopaminergic neurons (Greer et al 2005;Chang et al 2006).…”