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Published online 19 March 2001. doi:10.1083/jcb.152.6.1159
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© The Rockefeller University Press, 0021-9525/2001//1159 $5.00
The Journal of Cell Biology, Volume 152, Number 6, , 2001 1159-1168

Original Article

An Acidic Motif Retains Vesicular Monoamine Transporter 2 on Large Dense Core Vesicles



Clarissa L. Waitesa, Anand Mehtaa, Philip K. Tana, Gary Thomasb, Robert H. Edwardsa, and David E. Krantza

a Graduate Programs in Neuroscience and Cell Biology, Departments of Neurology and Physiology, University of California, San Francisco School of Medicine, San Francisco, California 94143-0435
b Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201
Graduate Programs in Neuroscience and Cell Biology, Departments of Neurology and Physiology, UCSF School of Medicine, 513 Parnassus Ave., San Francisco, CA 94143-0435.(415) 502-5687(415) 502-5687

edwards{at}itsa.ucsf.edu

The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of the vesicular monoamine transporter VMAT2 to LDCVs. We now find that a cluster of acidic residues including two serines phosphorylated by casein kinase 2 is required for the localization of VMAT2 to LDCVs. Deletion of the acidic cluster promotes the removal of VMAT2 from LDCVs during their maturation. The motif thus acts as a signal for retention on LDCVs. In addition, replacement of the serines by glutamate to mimic phosphorylation promotes the removal of VMAT2 from LDCVs, whereas replacement by alanine to prevent phosphorylation decreases removal. Phosphorylation of the acidic cluster thus appears to reduce the localization of VMAT2 to LDCVs by inactivating a retention mechanism.

Key Words: acidic cluster • large dense core vesicles • phosphorylation • VMAT2 • furin

© 2001 The Rockefeller University Press

Dr. Krantz's current address is Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA 90095.

Abbreviations used in this paper: BFA, brefeldin A; GST, glutathione-S-transferase; HA, hemagglutinin; LDCV, large dense core vesicle; PNS, post-nuclear supernatant; SgII, secretogranin II; SLMV, synaptic-like microvesicle; SV, synaptic vesicle.


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