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GTP-independent rapid and slow endocytosis at a central synapse

Nature Neuroscience volume 11, pages 45–53 (2008)Cite this article

Abstract

Vesicle endocytosis is essential for maintaining synaptic transmission. Its key step, membrane scission, is thought to be mediated by the GTPase dynamin in all forms of endocytosis at synapses. Our findings indicate that GTP-independent and probably dynamin-independent endocytosis co-exist with GTP- and dynamin-dependent endocytosis at the same synaptic nerve terminal, the calyx of Held, in rats. This previously undescribed form of endocytosis could be slow (tens of seconds) and/or rapid (a few seconds), similar to GTP- and dynamin-dependent endocytosis. It was activated during intense stimulation, whereas GTP- and dynamin-dependent endocytosis dominated during mild stimulation. These results establish a new model, in which vesicles are divided into two pools depending on their requirement for GTP and dynamin for retrieval. The GTP- and dynamin-dependent pool has higher priority for release and retrieval, but limited capacity, saturation of which leads to release and thus retrieval of GTP- and dynamin-independent vesicles.

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Figure 1: GTP- and dynamin-dependent rapid and slow endocytosis.
Figure 2: Dynamin-independent rapid and slow endocytosis.
Figure 3: Recovered endocytosis is associated with exocytosis during repetitive stim10.
Figure 4: Recovered endocytosis is associated with exocytosis during repetitive stimuli that mimic action potential trains.
Figure 5: Uptake of FM1-43 during dynamin-independent endocytosis.
Figure 6: Further characterization of recovered endocytosis.
Figure 7: Recovery of endocytosis in the presence of GTPγS depends on nerve activity.
Figure 8: Repetitive stimulation depletes a pool of vesicles that rely on GTP hydrolysis for retrieval and triggers recovered endocytosis.

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Acknowledgements

This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program.

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Author notes

  1. Benjamin McNeil and Wei Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bldg. 35, Rm. 2B-1012, Bethesda, 20892, Maryland, USA

    Jianhua Xu, Benjamin McNeil, Wei Wu, David Nees, Li Bai & Ling-Gang Wu

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  1. Jianhua Xu
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Contributions

J.X. and W.W. discovered the phenomenon. J.X. was involved in every aspect of the study, including experimental design, electrophysiology, FM dye imaging and data analysis. B.M. assisted in several experiments and designed the experiment for Supplementary Figure 4. W.W. carried out the experiments for Supplementary Figure 5. D.N. made the PH domain. L.B. performed the immunostaining. L.-G.W. supervised the project. L.-G.W and J.X. wrote the manuscript, with assistance from B.M.

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Correspondence to Ling-Gang Wu.

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Xu, J., McNeil, B., Wu, W. et al. GTP-independent rapid and slow endocytosis at a central synapse. Nat Neurosci 11, 45–53 (2008). https://doi.org/10.1038/nn2021

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