title: Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines.
abstract: The release of monoamine neurotransmitters from cell bodies and dendrites has an important role in behavior, but the mechanism (vesicular or non vesicular) has remained unclear. Because the location of vesicular monoamine transporter 2 (VMAT2) defines the secretory vesicles capable of monoamine release, we have studied its trafficking to assess the potential for monoamine release by exocytosis. In neuroendocrine PC12 cells, VMAT2 localizes exclusively to large dense-core vesicles (LDCVs), and we now show that cytoplasmic signals target VMAT2 directly to LDCVs within the biosynthetic pathway. In neurons, VMAT2 localizes to a population of vesicles that we now find undergo regulated exocytosis in dendrites. Although hippocampal neurons do not express typical LDCV proteins, transfected chromogranins A, B, and brain-derived neurotrophic factor (BDNF) colocalize with VMAT2. VMAT2 thus defines a population of secretory vesicles that mediate the activity-dependent somatodendritic release of multiple retrograde signals involved in synaptic function, growth, and plasticity.
authors.affiliation: Graduate Programs in Neuroscience and Cell Biology, Department of Neurology and Physiology, UCSF School of Medicine, 600 16th Street, San Francisco, California 94143, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: Clarissa L
authors.initials: CL
authors.lastname: Waites
authors.forename: Roland G
authors.initials: RG
authors.lastname: Staal
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Dobryy
authors.forename: Jeanna
authors.initials: J
authors.lastname: Park
authors.forename: David L
authors.initials: DL
authors.lastname: Sulzer
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001369:Axons / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D003593:Cytoplasm / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D021382:Protein Sorting Signals / Q000502:physiology*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D053379:Chromogranin A; D002864:Chromogranins; D021382:Protein Sorting Signals; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins