PMID- 29666153
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20190930
IS  - 1540-7748 (Electronic)
IS  - 0022-1295 (Print)
IS  - 0022-1295 (Linking)
VI  - 150
IP  - 5
DP  - 2018 May 7
TI  - The ins and outs of vesicular monoamine transporters.
PG  - 671-682
LID - 10.1085/jgp.201711980 [doi]
AB  - The H(+)-coupled vesicular monoamine transporter (VMAT) is a transporter 
      essential for life. VMAT mediates packaging of the monoamines serotonin, 
      dopamine, norepinephrine, and histamine from the neuronal cytoplasm into 
      presynaptic vesicles, which is a key step in the regulated release of 
      neurotransmitters. However, a detailed understanding of the mechanism of VMAT 
      function has been limited by the lack of availability of high-resolution 
      structural data. In recent years, a series of studies guided by homology models 
      has revealed significant insights into VMAT function, identifying residues that 
      contribute to the binding site and to specific steps in the transport cycle. 
      Moreover, to characterize the conformational transitions that occur upon binding 
      of the substrate and coupling ion, we have taken advantage of the unique and 
      powerful pharmacology of VMAT as well as of mutants that affect the 
      conformational equilibrium of the protein and shift it toward defined 
      conformations. This has allowed us to identify an important role for the proton 
      gradient in driving a shift from lumen-facing to cytoplasm-facing conformations.
CI  - (c) 2018 Yaffe et al.
FAU - Yaffe, Dana
AU  - Yaffe D
AD  - Department of Biological Chemistry, Alexander Silberman Institute of Life 
      Sciences, Hebrew University, Jerusalem, Israel dana.yaffe@mail.huji.ac.il.
FAU - Forrest, Lucy R
AU  - Forrest LR
AUID- ORCID: 0000-0003-1855-7985
AD  - Computational Structural Biology Section, National Institute of Neurological 
      Disorders and Stroke, National Institutes of Health, Bethesda, MD 
      lucy.forrest@nih.gov.
FAU - Schuldiner, Shimon
AU  - Schuldiner S
AUID- ORCID: 0000-0002-4874-6237
AD  - Department of Biological Chemistry, Alexander Silberman Institute of Life 
      Sciences, Hebrew University, Jerusalem, Israel shimon.schuldiner@huji.ac.il.
LA  - eng
SI  - PDB/3WDO
SI  - PDB/4YBQ
SI  - PDB/4YB9
GR  - R01 NS016708/NS/NINDS NIH HHS/United States
GR  - R56 NS016708/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180417
PL  - United States
TA  - J Gen Physiol
JT  - The Journal of general physiology
JID - 2985110R
RN  - 0 (Vesicular Monoamine Transport Proteins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Protein Domains
MH  - Vesicular Monoamine Transport Proteins/*chemistry/metabolism
PMC - PMC5940252
EDAT- 2018/04/19 06:00
MHDA- 2019/10/01 06:00
PMCR- 2018/11/07
CRDT- 2018/04/19 06:00
PHST- 2018/01/16 00:00 [received]
PHST- 2018/03/26 00:00 [accepted]
PHST- 2018/04/19 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/04/19 06:00 [entrez]
PHST- 2018/11/07 00:00 [pmc-release]
AID - jgp.201711980 [pii]
AID - 201711980 [pii]
AID - 10.1085/jgp.201711980 [doi]
PST - ppublish
SO  - J Gen Physiol. 2018 May 7;150(5):671-682. doi: 10.1085/jgp.201711980. Epub 2018 
      Apr 17.