The Vesicular Monoamine Transporters (VMATs): Role in the Chemical Coding of Neuronal Transmission and Monoamine Storage in Amine-Handling Immune and Inflammatory Cells
Monoamines can act as neurotransmitters, hormones, autocrine and paracrine factors, or autacoids. How they function depends on the locations of the cells that synthesize and store them, and the stimuli that release them. All amine transmitters are first sequestered in a storage vesicle or granule, from which they are secreted from the cell. This requires specific transporters that reside on the vesicle. All of the vesicular transporters for classical neurotransmitters inferred to exist as individual proteins based on functional studies, have been cloned and characterized in a detailed molecular way over the last ten years (see Table 1). As a result, an understanding has developed that the role of these transporters in the chemical coding of neurotransmission is dynamic, and a novel view of what constitutes a neurotransmitter phenotype for a given neuron has emerged. The purpose of this contribution is to highlight recent progress from our laboratories and others in understanding the evolution of vesicular transporter structure, transport properties and cell-specific expression, as these relate to the physiological and regulatory functions of mammalian monoamine-containing*** neuronal, endocrine, and hematopoietic cells.
KeywordsSynaptic Vesicle Vesicular Transporter Eccrine Sweat Gland Vesicular Monoamine Transporter Nucleus Tractus Solitarious
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- 2.R. G. Johnson Jr., Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport, Physiol. Revs. 68, 232–307 (1988).Google Scholar
- 9.E. Weihe, J.-H. Tao-Cheng, M. K.-H. Schäfer, J. D. Erickson, and L. E. Eiden, Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles, Proc. Natl. Acad. Sci. USA 93, 3547–3552 (1996).PubMedCrossRefGoogle Scholar
- 11.C. Sagné, S. E. Mestikaway, M.-F. Isambert, M. Hamon, J.-P. Nenry, B. Giros, and B. Gasnier, Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases, 417, 177–183(1997).Google Scholar
- 18.J. D. Erickson, H. Varoqui, M. Schäfer, M.-F. Diebler, E. Weihe, W. Modi, J. Rand, L. E. Eiden, T. I. Bonner, and T. Usdin, Functional characterization of the mammalian vesicular acetylcholine transporter and its expression from a ‘cholinergic’ gene locus, J. Biol. Chem. 269, 21929–21932 (1994).PubMedGoogle Scholar
- 24.D. Frisby, J. McManus, J. Duerr, and J. Rand, Regulation of cholinergic gene expression in C. elegans, Soc. Neurosci. Abstr. 22, 1032 (1996).Google Scholar
- 25.C. Eastman, H. R. Horvitz, and Y. S. Jin, Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-30 homeodomain protein, J. Neurosci. 9, 6225–6234 (1999).Google Scholar
- 26.J. J. Westmoreland, J. McEwen, B. A. Moore, Y. Jin, and B. G. Condie, Conserved function of C. elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation, J. Neurosci. in press, (2001).Google Scholar
- 29.J.-F. Brunet and A. Ghysen, Deconstructing cell determination: proneural genes and neuronal identity, Bio Essays 21, 313–318 (1999).Google Scholar
- 32.C.-H. Kim, H.-S. Kim, J. F. Cubells, and K.-S. Kim, A previously undescribed intron and extensive 5’ upstreamm sequence, but not Phox2a-mediated transactivation, are necessary for high level cell type- specific expression of the human norepinephrine transporter gene, J. Biol. Chem. 274, 6507–6518 (1999).PubMedCrossRefGoogle Scholar
- 49.I. S. Balan, M. V. Ugrumov, A. Calas, P. Mailly, M. Kreiger, and J. Thibault, Tyrosine hydroxylase- expressing and/or aromatic L-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of perinatal rats: differentiation and sexual dimorphism, J. Comp. Neurol. 425, 167–176 (2000).PubMedCrossRefGoogle Scholar
- 52.E. Weihe, M. Anlauf, M.-K. H. Schäfer, W. Hartschuh, and L. E. Eiden, VMAT2 is the transporter mediating sequestration of monoamines in rat and human platelets, mast cells, and cutaneous dendritic cells, Soc. Neurosci. Abstr. Nov. 7–12, #301.301 (1998).Google Scholar
- 55.A. Pletscher, M. Da Prada, K. H. Berneis, H. Steffen, B. Liitold, and H. G. Weder, Molecular organization f amine storage organelles of blood platelets and adrenal medulla, in Advances in Cytopharmacology, Ceccarelli, F. Clementi, and J. Meldolesi, Editors. 1974, Raven Press: New York. p. 257–264.Google Scholar