PMID- 30837287
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 132
IP  - 7
DP  - 2019 Apr 3
TI  - Drosophila Ptp4E regulates vesicular packaging for monoamine-neuropeptide 
      co-transmission.
LID - 10.1242/jcs.224568 [doi]
LID - jcs224568
AB  - Many neurons influence their targets through co-release of neuropeptides and 
      small-molecule transmitters. Neuropeptides are packaged into dense-core vesicles 
      (DCVs) in the soma and then transported to synapses, while small-molecule 
      transmitters such as monoamines are packaged by vesicular transporters that 
      function at synapses. These separate packaging mechanisms point to activity, by 
      inducing co-release as the sole scaler of co-transmission. Based on screening in 
      Drosophila for increased presynaptic neuropeptides, the receptor protein tyrosine 
      phosphatase (Rptp) Ptp4E was found to post-transcriptionally regulate 
      neuropeptide content in single DCVs at octopamine synapses. This occurs without 
      changing neuropeptide release efficiency, transport and DCV size measured by both 
      stimulated emission depletion super-resolution and transmission electron 
      microscopy. Ptp4E also controls the presynaptic abundance and activity of the 
      vesicular monoamine transporter (VMAT), which packages monoamine transmitters for 
      synaptic release. Thus, rather than rely on altering electrical activity, the 
      Rptp regulates packaging underlying monoamine-neuropeptide co-transmission by 
      controlling vesicular membrane transporter and luminal neuropeptide content.This 
      article has an associated First Person interview with the first author of the 
      paper.
CI  - (c) 2019. Published by The Company of Biologists Ltd.
FAU - Tao, Juan
AU  - Tao J
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh, 
      Pittsburgh, PA 15261, USA.
FAU - Bulgari, Dinara
AU  - Bulgari D
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh, 
      Pittsburgh, PA 15261, USA.
FAU - Berkhoudt, Drew A
AU  - Berkhoudt DA
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh, 
      Pittsburgh, PA 15261, USA.
FAU - Calderon, Michael J
AU  - Calderon MJ
AD  - Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
FAU - Watkins, Simon C
AU  - Watkins SC
AD  - Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
FAU - Fonseca Velez, Hector J
AU  - Fonseca Velez HJ
AUID- ORCID: 0000-0002-5159-0755
AD  - Department of Neuroscience, Universidad Central del Caribe, Bayamon, Puerto Rico 
      00960, USA.
FAU - Sabeva, Nadezhda
AU  - Sabeva N
AUID- ORCID: 0000-0002-7714-4884
AD  - Department of Neuroscience, Universidad Central del Caribe, Bayamon, Puerto Rico 
      00960, USA.
FAU - Deitcher, David L
AU  - Deitcher DL
AD  - Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, 
      USA.
FAU - Levitan, Edwin S
AU  - Levitan ES
AUID- ORCID: 0000-0003-3319-1344
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh, 
      Pittsburgh, PA 15261, USA elevitan@pitt.edu.
LA  - eng
GR  - R01 NS032385/NS/NINDS NIH HHS/United States
GR  - S10 OD021540/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190403
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Drosophila Proteins)
RN  - 0 (Neuropeptides)
RN  - EC 3.1.3.48 (Ptp4E protein, Drosophila)
RN  - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 4)
SB  - IM
MH  - Animals
MH  - Axons/physiology
MH  - Drosophila/*genetics
MH  - Drosophila Proteins/*genetics/physiology
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Male
MH  - Neurons/physiology
MH  - Neuropeptides/*physiology
MH  - Receptor-Like Protein Tyrosine Phosphatases, Class 4/*genetics/physiology
MH  - Secretory Vesicles/physiology
MH  - Synapses/physiology
MH  - Synaptic Vesicles/physiology
MH  - Transport Vesicles/*physiology
PMC - PMC6467486
OTO - NOTNLM
OT  - Neuropeptide vesicles
OT  - Secretory granules
OT  - Synaptic transmission
OT  - Tyrosine phosphatase
OT  - Vesicular transport
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2019/03/07 06:00
MHDA- 2020/06/26 06:00
PMCR- 2020/04/01
CRDT- 2019/03/07 06:00
PHST- 2018/08/30 00:00 [received]
PHST- 2019/02/25 00:00 [accepted]
PHST- 2019/03/07 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2019/03/07 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - jcs.224568 [pii]
AID - JCS224568 [pii]
AID - 10.1242/jcs.224568 [doi]
PST - epublish
SO  - J Cell Sci. 2019 Apr 3;132(7):jcs224568. doi: 10.1242/jcs.224568.