A leucine-based motif mediates the endocytosis of vesicular monoamine and acetylcholine transporters.

The Journal of Biological Chemistry
P K TanR H Edwards

Abstract

Specific transport proteins mediate the packaging of neurotransmitters into secretory vesicles and consequently require targeting to the appropriate intracellular compartment. To identify residues in the neuron-specific vesicular monoamine transporter (VMAT2) responsible for endocytosis, we examined the effect of amino (NH2-) and carboxyl (COOH-)-terminal mutations on steady state distribution and internalization. Deletion of a critical COOH-terminal domain sequence (AKEEKMAIL) results in accumulation of VMAT2 at the plasma membrane and a 50% reduction in endocytosis. Site-directed mutagenesis shows that replacement of the isoleucine-leucine pair within this sequence by alanine-alanine alone reduces endocytosis by 50% relative to wild type VMAT2. Furthermore, the KEEKMAIL sequence functions as an internalization signal when transferred to the plasma membrane protein Tac, and the mutation of the isoleucine-leucine pair also abolishes internalization of this protein. The closely related vesicular acetylcholine transporter (VAChT) contains a similar di-leucine sequence within the cytoplasmic COOH-terminal domain that when mutated results in accumulation of VAChT at the plasma membrane. The VAChT di-leucine sequence also confers in...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J D EricksonB J Hoffman
Jan 1, 1992·Methods in Enzymology·E SmytheS L Schmid
Jan 1, 1990·Annual Review of Physiology·P De Camilli, R Jahn
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Aug 1, 1994·Trends in Neurosciences·T Söllner, J E Rothman
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·M J NirenbergV M Pickel
Aug 25, 1995·The Journal of Biological Chemistry·L PondP A Peterson
Apr 1, 1995·Physiological Reviews·S SchuldinerM Linial
Oct 1, 1994·Current Opinion in Neurobiology·T F Martin
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·A RoghaniR H Edwards
Dec 1, 1993·Journal of Neurochemistry·J D Erickson, L E Eiden
Jan 1, 1993·Annual Review of Cell Biology·I S TrowbridgeC R Hopkins
Dec 1, 1995·The Journal of Cell Biology·K SteniusR Jahn
May 10, 1996·The Journal of Biological Chemistry·J DietrichC Geisler
Feb 1, 1996·The Journal of Cell Biology·E Grote, R B Kelly
May 1, 1996·The Journal of Cell Biology·F SimpsonM S Robinson
Mar 7, 1997·The Journal of Biological Chemistry·D E KrantzR H Edwards
Jan 1, 1997·Annual Review of Neuroscience·Y Liu, R H Edwards
Mar 21, 1997·Cell·M González-Gaitán, H Jäckle
Aug 15, 1997·The Journal of Biological Chemistry·C LamazeS L Schmid
Aug 1, 1994·Trends in Cell Biology·I V Sandoval, O Bakke

❮ Previous
Next ❯

Citations

Apr 24, 2001·Muscle & Nerve·E A Fon, R H Edwards
Dec 22, 1999·Biochemical and Biophysical Research Communications·M ItakuraM Takahashi
Feb 6, 2004·Journal of Neuroscience Methods·Janet WhitleyJoseph A Near
Jul 19, 2005·Neurobiology of Disease·Carol X-Q ChenYong-Jian Liu
Aug 15, 2002·Neurochemistry International·Marco A M PradoFernando G de Mello
Jul 30, 2011·Biochemistry·Jonathan J Sager, Gonzalo E Torres
Oct 25, 2012·Nature Communications·Kem A SochackiJustin W Taraska
Jan 27, 2010·The Journal of Biological Chemistry·Elena MarcelloIsabel Pérez-Otaño
Jan 8, 2010·The Journal of Biological Chemistry·Anna GrygorukDavid E Krantz
Aug 22, 2001·Molecular Biology of the Cell·H Zhao, M L Nonet
Nov 22, 2005·Infection and Immunity·Yue Zhang, Joseph T Barbieri
Dec 28, 1999·Annual Review of Cell and Developmental Biology·M J HannahW B Huttner
Jun 28, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Magda S SantosSusan M Voglmaier
Sep 21, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hajime HirasawaElio Raviola
Jun 11, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bibiana OnoaRobert H Edwards
Jun 28, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sarah M FossSusan M Voglmaier
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ester Fernández-SalasK Roger Aoki
Nov 8, 2011·Annual Review of Physiology·Thomas S Hnasko, Robert H Edwards
Feb 7, 2013·The Journal of Biological Chemistry·Mary A BittnerRonald W Holz
Mar 21, 2001·The Journal of Cell Biology·C L WaitesD E Krantz
Mar 6, 2012·Biochimica Et Biophysica Acta·Marta Koch, Matthew Holt
Aug 3, 2011·Neurobiology of Disease·Andrea C LoboCarlos B Duarte
May 13, 2008·Neuroscience·M S SantosS M Voglmaier
Apr 24, 2007·Current Opinion in Neurobiology·Susan M Voglmaier, Robert H Edwards
Nov 1, 2006·Progress in Neurobiology·Dario BonanomiFlavia Valtorta
Aug 12, 2005·Journal of Neurochemistry·Lucimar T FerreiraMarco A M Prado
Jun 15, 2005·Journal of Neurochemistry·Fabiola M RibeiroStephen S G Ferguson
May 30, 2008·Traffic·Hao FeiDavid E Krantz
Mar 10, 2006·Journal of Neurochemistry·Fabiola M RibeiroMarco A M Prado
Jun 6, 2007·Traffic·Nadja Jung, Volker Haucke
Mar 31, 2007·Journal of Neurochemistry·Hao FeiDavid E Krantz
Sep 8, 2009·Traffic·Tanja MaritzenVolker Haucke

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.