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Activity-dependent synaptic capture of transiting peptidergic vesicles

Nature Neuroscience volume 9, pages 896–900 (2006)Cite this article

Abstract

Synapses require resources synthesized in the neuronal soma, but there are no known mechanisms to overcome delays associated with the synthesis and axonal transport of new proteins generated in response to activity, or to direct resources specifically to active synapses. Here, in vivo imaging of the Drosophila melanogaster neuromuscular junction reveals a cell-biological strategy that addresses these constraints. Peptidergic vesicles continually transit through resting terminals, but retrograde peptidergic vesicle flux is accessed following activity to rapidly boost neuropeptide content in synaptic boutons. The presence of excess transiting vesicles implies that synaptic neuropeptide stores are limited by the capture of peptidergic vesicles at the terminal, rather than by synthesis in the soma or delivery via the axon. Furthermore, activity-dependent capture from a pool of transiting vesicles provides a nerve terminal–based mechanism for directing distally and slowly generated resources quickly to active synapses. Finally, retrograde transport in the nerve terminal is regulated by activity.

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Figure 1: Anterograde and retrograde transiting of DCVs.
Figure 2: Activity-induced neuropeptide accumulation in synaptic boutons.
Figure 3: Activity-dependent synaptic capture of DCVs.
Figure 4: Capture is reversible and repeatable.

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References

  1. Zupanc, G.K. Peptidergic transmission: from morphological correlates to functional implications. Micron 27, 35–91 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Burbach, J.P., Luckman, S.M., Murphy, D. & Gainer, H. Gene regulation in the magnocellular hypothalamo-neurohypophysial system. Physiol. Rev. 81, 1197–1267 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Taghert, P.H. & Veenstra, J.A. Drosophila neuropeptide signaling. Adv. Genet. 49, 1–65 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Nassel, D.R. Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones. Prog. Neurobiol. 68, 1–84 (2002).

    Article  PubMed  Google Scholar 

  5. Ahmari, S.E., Buchanan, J. & Smith, S.J. Assembly of presynaptic active zones from cytoplasmic transport packets. Nat. Neurosci. 3, 445–451 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Zhai, R.G. et al. Assembling the presynaptic active zone: a characterization of an active zone precursor vesicle. Neuron 29, 131–143 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Lessmann, V., Gottmann, K. & Malcangio, M. Neurotrophin secretion: current facts and future prospects. Prog. Neurobiol. 69, 341–374 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Pierce, J.P. & Milner, T.A. Parallel increases in synaptic and surface areas of mossy fiber terminals following seizure induction. Synapse 39, 249–256 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Murthy, V.N., Schikorski, T., Stevens, C.F. & Zhu, Y. Inactivity produces increases in neurotransmitter release and synapse size. Neuron 32, 673–682 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Brown, A. Axonal transport of membranous and nonmembranous cargoes: a unified perspective. J. Cell Biol. 160, 817–821 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shakiryanova, D., Tully, A., Hewes, R.S., Deitcher, D.L. & Levitan, E.S. Activity-dependent liberation of synaptic neuropeptide vesicles. Nat. Neurosci. 8, 173–178 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Rao, S., Lang, C., Levitan, E.S. & Deitcher, D.L. Visualization of neuropeptide expression, transport, and exocytosis in Drosophila melanogaster. J. Neurobiol. 49, 159–172 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Heifetz, Y. & Wolfner, M.F. Mating, seminal fluid components, and sperm cause changes in vesicle release in the Drosophila female reproductive tract. Proc. Natl. Acad. Sci. USA 101, 6261–6266 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Husain, Q.M. & Ewer, J. Use of targetable GFP-tagged neuropeptide for visualizing neuropeptide release following execution of a behavior. J. Neurobiol. 59, 181–191 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Mudher, A. et al. GSK-3β inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol. Psych. 9, 522–530 (2004).

    Article  CAS  Google Scholar 

  16. Sturman, D.A, Shakiryanova, D., Hewes, R.S., Deitcher, D.L. & Levitan, E.S. Nearly neutral secretory vesicles in Drosophila nerve terminals. Biophys. J. 90, L45–L47 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Atwood, H.L., Govind, C.K. & Wu, C.F. Differential ultrastructure of synaptic terminals on ventral longitudinal abdominal muscles in Drosophila larvae. J. Neurobiol. 24, 1008–1024 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Jia, X.X., Gorczyca, M. & Budnik, V. Ultrastructure of neuromuscular junctions in Drosophila: comparison of wild type and mutants with increased excitability. J. Neurobiol. 24, 1025–1044 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Levitan, E.S. Studying neuronal peptide release and secretory granule dynamics with green fluorescent protein. Methods 16, 182–187 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Krueger, S.R., Kolar, A. & Fitzsimonds, R.M. The presynaptic release apparatus is functional in the absence of dendritic contact and highly mobile within isolated axons. Neuron 40, 945–957 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Darcy, K.J., Staras, K., Collinson, L.M. & Goda, Y. Constitutive sharing of recycling synaptic vesicles between presynaptic boutons. Nat. Neurosci. 9, 315–321 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Neubig, R. The time course of drug action. in Principles of Drug Action. 3rd edn. (eds. Pratt, W.B. & Taylor, P.) 311–313 (Churchill-Livingstone, London, 1990).

    Google Scholar 

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Acknowledgements

We thank W.C. DeGroat and K. Kandler for their comments. This research was supported by grant NS32385 from the US National Institutes of Health to E.S.L.

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Author notes

  1. Arvonn Tully

    Present address: Compix Inc., 109 Nicholson Road, Cranberry, Pennsylvania, 15143, USA

Authors and Affiliations

  1. Department of Pharmacology, University of Pittburgh, Pittsburgh, Pennsylvania, 15261, USA

    Dinara Shakiryanova, Arvonn Tully & Edwin S Levitan

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  1. Dinara Shakiryanova
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Correspondence to Edwin S Levitan.

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Supplementary information

Supplementary Fig. 1

Constitutive replacement of synaptic DCVs is slow. (PDF 137 kb)

Supplementary Fig. 2

Detection of vesicle shipments. (PDF 73 kb)

Supplementary Fig. 3

Movement of vesicle shipments. (PDF 189 kb)

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Shakiryanova, D., Tully, A. & Levitan, E. Activity-dependent synaptic capture of transiting peptidergic vesicles. Nat Neurosci 9, 896–900 (2006). https://doi.org/10.1038/nn1719

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