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Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals
Edited by Eve Marder, Brandeis University, Waltham, MA, and approved January 24, 2014 (received for review November 26, 2013)

Significance
Neuropeptides, which affect mood and behavior, are synthesized in the soma and delivered to nerve terminals for storage and release. Yet, among identified neurons, there is great variation in the abundance of neuropeptides in terminals. Demonstrated transcriptional regulation of neuropeptide synthesis supports the view that presynaptic neuropeptide stores are proportional to synthesis-driven delivery of neuropeptide-containing vesicles to terminals. However, we show that nerve terminals with dramatically different neuropeptide stores are supported by identical vesicle delivery and differ instead in efficiency of vesicle capture. Vesicle capture in the terminal is under transcriptional control and influences vesicle distribution and replacement as well as neuropeptide accumulation for release. Thus, vesicle capture is a major determinant of nerve terminal function.
Abstract
Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: elevitan{at}pitt.edu.
Author contributions: D.B. and E.S.L. designed research; D.B. performed research; C.Z., R.S.H., and D.L.D. contributed new reagents/analytic tools; D.B. and E.S.L. analyzed data; and D.B. and E.S.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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- Neuroscience