Open AccessPtp4E regulates vesicular packaging for monoamine-neuropeptide co-transmission
Author(s) -
Juan Tao,
Dinara Bulgari,
Drew A Berkhoudt,
Michael Calderon,
Simon C. Watkins,
Hector J Fonseca Velez,
Nadezhda S. Sabeva,
David L. Deitcher,
Edwin S. Levitan
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.224568
Subject(s) - monoamine neurotransmitter , vesicular monoamine transporter , biology , neuropeptide , microbiology and biotechnology , neurotransmission , synaptic vesicle , vesicular transport protein , neuropeptide y receptor , vesicle , vesicular monoamine transporter 2 , biochemistry , serotonin , receptor , membrane
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 STED super-resolution and transmission electron microscopy. Ptp4E also controls 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.