An acidic motif retains vesicular monoamine transporter 2 on large dense core vesicles.
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.
Graduate Program in Neuroscience, Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, California 94143-0435, USA.
C L
CL
Waites
A
A
Mehta
P K
PK
Tan
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G
Thomas
R H
RH
Edwards
D E
DE
Krantz
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015306:Biogenic Monoamines / Q000737:chemistry / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002458:Cell Fractionation; D002864:Chromogranins; D005089:Exocytosis / Q000502:physiology*; D006023:Glycoproteins; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009479:Neuropeptides; D016716:PC12 Cells; D010766:Phosphorylation; D021382:Protein Sorting Signals; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins; D021601:trans-Golgi Network / Q000378:metabolism
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D002864:Chromogranins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C491914:PACS1 protein, human; C113943:Pacs1 protein, rat; D021382:Protein Sorting Signals; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; C493454:Slc18a2 protein, rat; C513045:Tgoln2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins; D020126:Brefeldin A