1. Cell Biology
  2. Neuroscience
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Synaptojanin cooperates in vivo with endophilin through an unexpected mechanism

  1. Yongming Dong
  2. Yueyang Gou
  3. Yi Li
  4. Yan Liu
  5. Jihong Bai  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
  2. Sichuan University, China
Research Article
  • Cited 22
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Cite this article as: eLife 2015;4:e05660 doi: 10.7554/eLife.05660

Abstract

Synaptojanin and endophilin represent a classic pair of endocytic proteins that exhibit coordinated action during rapid synaptic vesicle (SV) endocytosis. Current models suggest that synaptojanin activity is tightly associated with endophilin through high-affinity binding between the synaptojanin proline-rich domain (PRD) and the endophilin SH3 domain. Surprisingly, we find that truncated synaptojanin lacking the PRD domain sustains normal synaptic transmission, indicating that synaptojanin's core function in vivo resides in the remaining two domains that contain phosphoinositide phosphatase activities: an N-terminal Sac1 phosphatase domain and a 5-phosphatase domain. We further show that the Sac1 domain plays an unexpected role in targeting synaptojanin to synapses. The requirement for Sac1 is bypassed by tethering the synaptojanin 5-phophatase to the endophilin membrane-bending BAR domain. Together, our results uncover an unexpected role for the Sac1 domain in vivo in supporting coincident action between synaptojanin and endophilin at synapses.

Article and author information

Author details

  1. Yongming Dong

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yueyang Gou

    College of Life Science, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yi Li

    College of Life Science, Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yan Liu

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jihong Bai

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    jbai@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Publication history

  1. Received: November 18, 2014
  2. Accepted: April 27, 2015
  3. Accepted Manuscript published: April 28, 2015 (version 1)
  4. Version of Record published: May 18, 2015 (version 2)

Copyright

© 2015, Dong 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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