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PMID:15860731

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Citation

Salazar, G, Craige, B, Love, R, Kalman, D and Faundez, V (2005) Vglut1 and ZnT3 co-targeting mechanisms regulate vesicular zinc stores in PC12 cells. J. Cell. Sci. 118:1911-21

Abstract

The lumenal ionic content of an organelle is determined by its complement of channels and transporters. These proteins reach their resident organelles by adaptor-dependent mechanisms. This concept is illustrated in AP-3 deficiencies, in which synaptic vesicle zinc is depleted because the synaptic-vesicle-specific zinc transporter 3 does not reach synaptic vesicles. However, whether zinc transporter 3 is the only membrane protein defining synaptic-vesicle zinc content remains unknown. To address this question, we examined whether zinc transporter 3 and the vesicular glutamate transporter Vglut1 (a transporter that coexists with zinc transporter 3 in brain nerve terminals) were co-targeted to synaptic-like microvesicle fractions in PC12 cells. Deconvolution microscopy and subcellular fractionation demonstrated that these two transporters were present on the same vesicles in PC12 cells. Vglut1 content in synaptic-like microvesicle fractions and brain synaptic vesicles was partially sensitive to pharmacological and genetic perturbation of AP-3 function. Whole-cell flow-cytometry analysis of PC12 cell lines expressing zinc transporter 3, Vglut1 or both showed that vesicular zinc uptake was increased by Vglut1 expression. Conversely, production of zinc transporter 3 increased the vesicular uptake of glutamate in a zinc-dependent fashion. Our results suggest that the coupling of zinc transporter 3 and Vglut1 transport mechanisms regulates neurotransmitter content in secretory vesicles.

Links

PubMed Online version:10.1242/jcs.02319

Keywords

Animals; Biological Transport; Brain/metabolism; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cation Transport Proteins/metabolism; Cation Transport Proteins/pharmacokinetics; Dose-Response Relationship, Drug; Flow Cytometry; Glutamic Acid/chemistry; Ions; Membrane Proteins/metabolism; Membrane Proteins/physiology; Membrane Transport Proteins/metabolism; Membrane Transport Proteins/physiology; Microscopy, Fluorescence; PC12 Cells; Plasmids/metabolism; Protein Transport; Rats; Subcellular Fractions/chemistry; Synapses/metabolism; Synaptic Vesicles/metabolism; Vesicular Glutamate Transport Protein 1; Zinc/chemistry; Zinc/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AP3D1

acts_upstream_of_or_within

GO:0033365: protein localization to organelle

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856083

P

Seeded From UniProt

complete

MOUSE:AP3D1

acts_upstream_of_or_within

GO:0048499: synaptic vesicle membrane organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856083

P

  • occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:ZNT3

located_in

GO:0030672: synaptic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ZNT3

acts_upstream_of_or_within

GO:0051050: positive regulation of transport

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1920211

P

Seeded From UniProt

complete

MOUSE:VGLU1

located_in

GO:0030672: synaptic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:VGLU1

acts_upstream_of_or_within

GO:0051938: L-glutamate import

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:VGLU1

acts_upstream_of_or_within

GO:0051938: L-glutamate import

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1345280

P

Seeded From UniProt

complete

MOUSE:VGLU1

part_of

GO:0030672: synaptic vesicle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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