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J Cell Sci. 2019 Apr 3;132(7). pii: jcs224568. doi: 10.1242/jcs.224568.

Drosophila Ptp4E regulates vesicular packaging for monoamine-neuropeptide co-transmission.

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Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Neuroscience, Universidad Central del Caribe, Bayamón, Puerto Rico 00960, USA.
Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA


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.


Neuropeptide vesicles; Secretory granules; Synaptic transmission; Tyrosine phosphatase; Vesicular transport

[Available on 2020-04-01]
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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