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A positive feedback loop between Flower and PI(4,5)P2 at periactive zones controls bulk endocytosis in Drosophila

  1. Chi-Kuang Yao  Is a corresponding author
  2. Tsai-Ning Li
  3. Yu-Jung Chen
  4. You-Tung Wang
  5. Hsin-Chieh Lin
  6. Ting-Yi Lu
  1. Academia Sinica, Taiwan
  2. Academia Sinica, Taiwan, Republic of China
Research Article
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Cite this article as: eLife 2020;9:e60125 doi: 10.7554/eLife.60125

Abstract

Synaptic vesicle (SV) endocytosis is coupled to exocytosis to maintain SV pool size and thus neurotransmitter release. Intense stimulation induces activity-dependent bulk endocytosis (ADBE) to recapture large quantities of SV constituents in large endosomes from which SVs reform. How these consecutive processes are spatiotemporally coordinated remains unknown. Here, we show that Flower Ca2+ channel-dependent phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) compartmentalization governs control of these processes in Drosophila. Strong stimuli trigger PI(4,5)P2 microdomain formation at periactive zones. Upon exocytosis, Flower translocates from SVs to periactive zones, where it increases PI(4,5)P2 levels via Ca2+ influxes. Remarkably, PI(4,5)P2 directly enhances Flower channel activity, thereby establishing a positive feedback loop for PI(4,5)P2 microdomain compartmentalization. PI(4,5)P2 microdomains drive ADBE and SV reformation from bulk endosomes. PI(4,5)P2 further retrieves Flower to bulk endosomes, terminating endocytosis. We propose that the interplay between Flower and PI(4,5)P2 is the crucial spatiotemporal cue that couples exocytosis to ADBE and subsequent SV reformation.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided.

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Author details

  1. Chi-Kuang Yao

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    For correspondence
    ckyao@gate.sinica.edu.tw
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0977-4347
  2. Tsai-Ning Li

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0195-145X
  3. Yu-Jung Chen

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  4. You-Tung Wang

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  5. Hsin-Chieh Lin

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ting-Yi Lu

    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministry of Science and Technology, Taiwan (107-2311-B-001-003-MY3)

  • Chi-Kuang Yao

Ministry of Science and Technology, Taiwan (106-0210-01-15-02)

  • Chi-Kuang Yao

Ministry of Science and Technology, Taiwan (107-0210-01-19-01)

  • Chi-Kuang Yao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: June 17, 2020
  2. Accepted: December 9, 2020
  3. Accepted Manuscript published: December 10, 2020 (version 1)
  4. Version of Record published: December 18, 2020 (version 2)

Copyright

© 2020, Yao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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