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

Romero-Calderón R, Uhlenbrock G, Borycz J, Simon AF, Grygoruk A, Yee SK, Shyer A, Ackerson LC, Maidment NT, Meinertzhagen IA, Hovemann BT, Krantz DE - PLoS Genet. (2008)

Bottom Line: In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines.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.Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

View Article: PubMed Central - PubMed

Affiliation: Gonda Goldschmied Center for Neuroscience and Genetics Research, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.

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.

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Related in: MedlinePlus

The antibody to DVMAT-A+B labels the optic neuropiles.(A) Projected confocal image of whole w adult brain labeled with the antibody against the N-terminus of DVMAT (anti-N) that recognizes both DVMAT-A and -B. The entire surface of the lamina is labeled with anti-N in a honeycomb pattern (white arrows). In the central brain, cell bodies (asterisk) and a large number of processes are labeled, consistent with the previously described expression of DVMAT-A. Additional punctate labeling in the lamina (B) (arrowheads) is likely to represent previously described serotonergic varicosities, more easily seen in a single optical section of the lamina (B) (arrowheads) and in a tangential section through the lamina (C) (La, see arrowheads) and distal medulla (C) (Me). Labeling of the lamina surface is also apparent (C) (arrows) in the tangential view of the lamina and distal medulla. (D–F) Cryostat sections of w adult brains labeled for Repo (green) and DVMAT-A+B (magenta). Repo label in glial cell nuclei of the optic lobe and central brain does not co-localize with the label for DVMAT-A+B, but the DVMAT-A+B label in the distal lamina appears to co-localize with glial cell nuclei (D) (arrow) (overlap shown in F). Bars: (A) 50 microns, (B,C) 25 microns, (D–F) 50 microns.
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pgen-1000245-g003: The antibody to DVMAT-A+B labels the optic neuropiles.(A) Projected confocal image of whole w adult brain labeled with the antibody against the N-terminus of DVMAT (anti-N) that recognizes both DVMAT-A and -B. The entire surface of the lamina is labeled with anti-N in a honeycomb pattern (white arrows). In the central brain, cell bodies (asterisk) and a large number of processes are labeled, consistent with the previously described expression of DVMAT-A. Additional punctate labeling in the lamina (B) (arrowheads) is likely to represent previously described serotonergic varicosities, more easily seen in a single optical section of the lamina (B) (arrowheads) and in a tangential section through the lamina (C) (La, see arrowheads) and distal medulla (C) (Me). Labeling of the lamina surface is also apparent (C) (arrows) in the tangential view of the lamina and distal medulla. (D–F) Cryostat sections of w adult brains labeled for Repo (green) and DVMAT-A+B (magenta). Repo label in glial cell nuclei of the optic lobe and central brain does not co-localize with the label for DVMAT-A+B, but the DVMAT-A+B label in the distal lamina appears to co-localize with glial cell nuclei (D) (arrow) (overlap shown in F). Bars: (A) 50 microns, (B,C) 25 microns, (D–F) 50 microns.

Mentions: To determine the identity of the cells expressing DVMAT-B, we first performed additional experiments using the anti-N antibody directed against the N-terminus of DVMAT. Since the N-terminus of DVMAT is common to both DVMAT-A and B, labeling using anti-N showed the expression of both isoforms (DVMAT-A+B) and allowed the simultaneous visualization of both patterns of expression. In Figure 3A, labeling with anti-N in whole-mounts of the entire brain revealed a punctate pattern in the central brain and medulla as well as scattered cell bodies. This pattern was similar if not identical to the labeling in the adult brain we previously observed using an antibody specific for DVMAT-A [40]. Labeling with DVMAT-A also showed a punctate pattern in the lamina that represents projections from the LP2 cluster of serotonergic neurons [40]. Using anti-N to label DVMAT-A+B, we observed a similar punctate labeling pattern in the lamina (Figure 3A and 3B); however, unlike the pattern we saw using the antibody to DVMAT-A, the entire surface of the lamina was labeled by anti-N (Figure 3A, see also Figure 3C). These data are consistent with the expression pattern of DVMAT-B in the distal lamina that we observed using the anti-B antibodies.


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

Romero-Calderón R, Uhlenbrock G, Borycz J, Simon AF, Grygoruk A, Yee SK, Shyer A, Ackerson LC, Maidment NT, Meinertzhagen IA, Hovemann BT, Krantz DE - PLoS Genet. (2008)

The antibody to DVMAT-A+B labels the optic neuropiles.(A) Projected confocal image of whole w adult brain labeled with the antibody against the N-terminus of DVMAT (anti-N) that recognizes both DVMAT-A and -B. The entire surface of the lamina is labeled with anti-N in a honeycomb pattern (white arrows). In the central brain, cell bodies (asterisk) and a large number of processes are labeled, consistent with the previously described expression of DVMAT-A. Additional punctate labeling in the lamina (B) (arrowheads) is likely to represent previously described serotonergic varicosities, more easily seen in a single optical section of the lamina (B) (arrowheads) and in a tangential section through the lamina (C) (La, see arrowheads) and distal medulla (C) (Me). Labeling of the lamina surface is also apparent (C) (arrows) in the tangential view of the lamina and distal medulla. (D–F) Cryostat sections of w adult brains labeled for Repo (green) and DVMAT-A+B (magenta). Repo label in glial cell nuclei of the optic lobe and central brain does not co-localize with the label for DVMAT-A+B, but the DVMAT-A+B label in the distal lamina appears to co-localize with glial cell nuclei (D) (arrow) (overlap shown in F). Bars: (A) 50 microns, (B,C) 25 microns, (D–F) 50 microns.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2570955&req=5

pgen-1000245-g003: The antibody to DVMAT-A+B labels the optic neuropiles.(A) Projected confocal image of whole w adult brain labeled with the antibody against the N-terminus of DVMAT (anti-N) that recognizes both DVMAT-A and -B. The entire surface of the lamina is labeled with anti-N in a honeycomb pattern (white arrows). In the central brain, cell bodies (asterisk) and a large number of processes are labeled, consistent with the previously described expression of DVMAT-A. Additional punctate labeling in the lamina (B) (arrowheads) is likely to represent previously described serotonergic varicosities, more easily seen in a single optical section of the lamina (B) (arrowheads) and in a tangential section through the lamina (C) (La, see arrowheads) and distal medulla (C) (Me). Labeling of the lamina surface is also apparent (C) (arrows) in the tangential view of the lamina and distal medulla. (D–F) Cryostat sections of w adult brains labeled for Repo (green) and DVMAT-A+B (magenta). Repo label in glial cell nuclei of the optic lobe and central brain does not co-localize with the label for DVMAT-A+B, but the DVMAT-A+B label in the distal lamina appears to co-localize with glial cell nuclei (D) (arrow) (overlap shown in F). Bars: (A) 50 microns, (B,C) 25 microns, (D–F) 50 microns.
Mentions: To determine the identity of the cells expressing DVMAT-B, we first performed additional experiments using the anti-N antibody directed against the N-terminus of DVMAT. Since the N-terminus of DVMAT is common to both DVMAT-A and B, labeling using anti-N showed the expression of both isoforms (DVMAT-A+B) and allowed the simultaneous visualization of both patterns of expression. In Figure 3A, labeling with anti-N in whole-mounts of the entire brain revealed a punctate pattern in the central brain and medulla as well as scattered cell bodies. This pattern was similar if not identical to the labeling in the adult brain we previously observed using an antibody specific for DVMAT-A [40]. Labeling with DVMAT-A also showed a punctate pattern in the lamina that represents projections from the LP2 cluster of serotonergic neurons [40]. Using anti-N to label DVMAT-A+B, we observed a similar punctate labeling pattern in the lamina (Figure 3A and 3B); however, unlike the pattern we saw using the antibody to DVMAT-A, the entire surface of the lamina was labeled by anti-N (Figure 3A, see also Figure 3C). These data are consistent with the expression pattern of DVMAT-B in the distal lamina that we observed using the anti-B antibodies.

Bottom Line: In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines.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.Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

View Article: PubMed Central - PubMed

Affiliation: Gonda Goldschmied Center for Neuroscience and Genetics Research, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus