Intact synapse structure and function after combined knockout of PTPδ, PTPσ and LAR

  1. Javier Emperador-Melero  Is a corresponding author
  2. Giovanni de Nola
  3. Pascal S Kaeser  Is a corresponding author
  1. Harvard Medical School, United States

Abstract

It has long been proposed that Leukocyte common Antigen-Related Receptor Protein Tyrosine Phosphatases (LAR-RPTPs) are cell-adhesion proteins that control synapse assembly. Their synaptic nanoscale localization, however, is not established, and synapse fine structure after knockout of the three vertebrate LAR-RPTPs (PTPδ, PTPσ and LAR) has not been tested. Here, superresolution microscopy reveals that PTPδ localizes to the synaptic cleft precisely apposed to postsynaptic scaffolds of excitatory and inhibitory synapses. We next assessed synapse structure in newly generated triple-conditional knockout mice for PTPδ, PTPσ and LAR, complementing a recent independent study of synapse function after LAR-RPTP ablation (Sclip and Südhof, 2020). While mild effects on synaptic vesicle clustering and active zone architecture were detected, synapse numbers and their overall structure were unaffected, membrane anchoring of the active zone persisted, and vesicle docking and release were normal. Hence, despite their localization at synaptic appositions, LAR-RPTPs are dispensable for presynapse structure and function.

Data availability

Data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Javier Emperador-Melero

    Department of Neurobiology, Harvard Medical School, Boston, United States
    For correspondence
    Javier_EmperadorMelero@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Giovanni de Nola

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Pascal S Kaeser

    Department of Neurobiology, Harvard Medical School, Boston, United States
    For correspondence
    kaeser@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1558-1958

Funding

National Institute of Mental Health (R01MH113349)

  • Pascal S Kaeser

National Institute of Neurological Disorders and Stroke (R01NS083898)

  • Pascal S Kaeser

Harvard Medical School

  • Pascal S Kaeser

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

Ethics

Animal experimentation: All animal experiments were performed according to institutional guidelines of Harvard University, and were in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animals were handled according to protocols (protocol number IS00000049) approved by the institutional animal care and use committee (IACUC).

Reviewing Editor

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

Publication history

  1. Received: January 18, 2021
  2. Accepted: February 28, 2021
  3. Accepted Manuscript published: March 3, 2021 (version 1)
  4. Version of Record published: March 16, 2021 (version 2)

Copyright

© 2021, Emperador-Melero 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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  1. Javier Emperador-Melero
  2. Giovanni de Nola
  3. Pascal S Kaeser
(2021)
Intact synapse structure and function after combined knockout of PTPδ, PTPσ and LAR
eLife 10:e66638.
https://doi.org/10.7554/eLife.66638

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