PMID- 17217417
OWN - NLM
STAT- MEDLINE
DCOM- 20070402
LR  - 20071203
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 100
IP  - 5
DP  - 2007 Mar
TI  - The vesicular monoamine transporter 2 contains trafficking signals in both its 
      N-glycosylation and C-terminal domains.
PG  - 1387-96
AB  - The vesicular acetylcholine transporter (VAChT) and the vesicular monoamine 
      transporter (VMAT) belong to the same transporter family that packages 
      acetylcholine into synaptic vesicles (SVs) and biogenic amines into large dense 
      core vesicles (LDCVs) and/or SVs, respectively. These transporters share 
      similarities in sequence and structure with their N- and C-terminal domains 
      located in the cytoplasm. When expressed in PC12 cells, VMAT2 localizes to LDCV, 
      whereas VAChT is found mainly on synaptic-like microvesicles. Previous studies 
      have shown that the cytoplasmic C-terminal domain of VAChT contains signals 
      targeting this transporter to SVs. However, the targeting signals for VMAT have 
      not been completely elucidated. To identify signals targeting VMAT2 to LDCV, the 
      subcellular localization of VMAT2-VAChT chimeras was analyzed in PC12 cells. 
      Chimeras having either the N-terminal region through transmembrane domain 2 of 
      VMAT2 or the C-terminal domain of VMAT2 do not traffic to LDCV efficiently. In 
      contrast, chimeras having both of these regions, or the luminal glycosylated loop 
      in conjunction with transmembrane domains 1 and 2 and the C-terminal domain of 
      VMAT2, traffic to LDCV. Treatment of PC12 cells with 1-deoxymannojirimycin, a 
      specific alpha-mannosidase I inhibitor, causes VMAT2 to localize to synaptic-like 
      microvesicles. The results indicate that both mature N-linked glycosylation and 
      the C-terminus are important for proper trafficking of VMAT2 and that the 
      locations of trafficking signals in VMAT2 and VAChT are surprisingly different.
FAU - Yao, Jia
AU  - Yao J
AD  - Department of Molecular and Cellular Biochemistry, University of Kentucky, 
      Lexington, Kentucky 40536-0509, USA.
FAU - Hersh, Louis B
AU  - Hersh LB
LA  - eng
GR  - AG05893/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070108
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Slc18a2 protein, rat)
RN  - 0 (Vesicular Acetylcholine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
SB  - IM
MH  - Animals
MH  - Glycosylation
MH  - PC12 Cells
MH  - *Protein Sorting Signals
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Vesicular Acetylcholine Transport Proteins/genetics/metabolism
MH  - Vesicular Monoamine Transport Proteins/genetics/*metabolism
EDAT- 2007/01/16 09:00
MHDA- 2007/04/03 09:00
CRDT- 2007/01/16 09:00
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2007/04/03 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
AID - JNC4326 [pii]
AID - 10.1111/j.1471-4159.2006.04326.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Mar;100(5):1387-96. doi: 10.1111/j.1471-4159.2006.04326.x. Epub 
      2007 Jan 8.