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The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine

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Abstract

The vesicular amine transporters (VATs) are expressed as integral proteins of the lipid bilayer membrane of secretory vesicles in neuronal and endocrine cells. Their function is to allow the transport of acetylcholine (by the vesicular acetylcholine transporter VAChT; SLC18A3) and biogenic amines (by the vesicular monoamine transporters VMAT1 and VMAT2; SLC18A1 and SLC18A2) into secretory vesicles, which then discharge them into the extracellular space by exocytosis. Transport of positively charged amines by members of the SLC18 family in all cases utilizes an electrochemical gradient across the vesicular membrane established by proton pumping into the vesicle via a vacuolar ATPase; the amine is accumulated in the vesicle at the expense of the proton gradient, at a ratio of one translocated amine per two translocated protons. The members of the SLC18 family have become important histochemical markers for chemical coding in neuroendocrine tissues and cells. The structural basis of their remarkable ability to transport positively charged amines against a very large concentration gradient, as well as potential disease association with impaired transporter function and expression, are under intense investigation.

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Notes

  1. *Note added in proof: VMAT2 is expressed in human pancreatic endocrine cells containing insulin but absent from islet cells expressing glucagon, somatostatin or pancreatic polypeptide [Anlauf M, Eissele R, Schäfer MK-H, Eiden LE, Arnold R, Pauser U, Klöppel G, Weihe E (2003) Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. J Histochem Cytochem (In press)].

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Authors and Affiliations

  1. Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Building 36, Room 2A-11, 9000 Rockville Pike, Bethesda, MD 20892, USA

    Lee E. Eiden

  2. Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Robert-Koch-Strasse 6, 35033, Marburg, Germany

    Martin K.-H. Schäfer & Eberhard Weihe

  3. Laboratory of Molecular Neurobiology, Clinic for Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany

    Burkhard Schütz

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  1. Lee E. Eiden
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  2. Martin K.-H. Schäfer
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  3. Eberhard Weihe
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  4. Burkhard Schütz
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Correspondence to Lee E. Eiden.

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Eiden, L.E., Schäfer, M.KH., Weihe, E. et al. The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine. Pflugers Arch - Eur J Physiol 447, 636–640 (2004). https://doi.org/10.1007/s00424-003-1100-5

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  • DOI: https://doi.org/10.1007/s00424-003-1100-5

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