TMEM95 is a sperm membrane protein essential for mammalian fertilization

  1. Ismael Lamas-Toranzo
  2. Julieta G Hamze
  3. Enrica Bianchi
  4. Beatriz Fernández-Fuertes
  5. Serafín Pérez-Cerezales
  6. Ricardo Laguna-Barraza
  7. Raúl Fernández-González
  8. Pat Lonergan
  9. Alfonso Gutiérrez-Adán
  10. Gavin J Wright
  11. María Jiménez-Movilla  Is a corresponding author
  12. Pablo Bermejo-Álvarez  Is a corresponding author
  1. INIA, Spain
  2. University of Murcia, Spain
  3. Wellcome Trust Sanger Institute, United Kingdom
  4. University of Girona, Spain
  5. University College Dublin, Ireland

Abstract

The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.

Data availability

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

Article and author information

Author details

  1. Ismael Lamas-Toranzo

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7790-2649
  2. Julieta G Hamze

    Department of Cell Biology and Histology, University of Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Enrica Bianchi

    Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Beatriz Fernández-Fuertes

    Department of Biology, University of Girona, Girona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Serafín Pérez-Cerezales

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Ricardo Laguna-Barraza

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Raúl Fernández-González

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Pat Lonergan

    School of Agriculture and Food Science, University College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  9. Alfonso Gutiérrez-Adán

    Animal Reproduction, INIA, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Gavin J Wright

    Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0537-0863
  11. María Jiménez-Movilla

    Department of Cell Biology and Histology, University of Murcia, Murcia, Spain
    For correspondence
    mariajm@um.es
    Competing interests
    The authors declare that no competing interests exist.
  12. Pablo Bermejo-Álvarez

    Animal Reproduction, INIA, Madrid, Spain
    For correspondence
    bermejo.pablo@inia.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9907-2626

Funding

Ministerio de Economía y Competitividad (RYC-2012-10193)

  • Pablo Bermejo-Álvarez

Ministerio de Economía y Competitividad (FPI fellowship)

  • Ismael Lamas-Toranzo

Ministerio de Economía y Competitividad (Ramón y Cajal contract)

  • Serafín Pérez-Cerezales

European Union Seventh Framework Programme (Marie Curie fellowship)

  • Beatriz Fernández-Fuertes

Medical Research Council (MR/M012468/1)

  • Enrica Bianchi
  • Gavin J Wright

Ministerio de Economía y Competitividad (AGL2014-58739-R)

  • Pablo Bermejo-Álvarez

Ministerio de Economía y Competitividad (AGL2017-84908-R)

  • Pablo Bermejo-Álvarez

Ministerio de Economía y Competitividad (AGL2015-70159-P)

  • María Jiménez-Movilla

Ministerio de Economía y Competitividad (RTI2018-093548-B-I00)

  • Alfonso Gutiérrez-Adán

Ministerio de Economía y Competitividad (AGL2016-71890-REDT)

  • Alfonso Gutiérrez-Adán
  • María Jiménez-Movilla
  • Pablo Bermejo-Álvarez

H2020 European Research Council (StG 757886-ELONGAN)

  • Pablo Bermejo-Álvarez

Fundación Séneca-Agencia de Ciencia y Tecnología de Murcia (20887/PI/18)

  • María Jiménez-Movilla

Department of Agriculture, Food and the Marine (11/S/104)

  • Pat Lonergan

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

Reviewing Editor

  1. Polina V Lishko, University of California, Berkeley, United States

Ethics

Animal experimentation: All experimental procedures were approved by INIA Animal Care Committee and Madrid Region Authorities (PROEX 040/17) in agreement with European legislation.

Version history

  1. Received: November 24, 2019
  2. Accepted: June 1, 2020
  3. Accepted Manuscript published: June 2, 2020 (version 1)
  4. Version of Record published: June 15, 2020 (version 2)

Copyright

© 2020, Lamas-Toranzo 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. Ismael Lamas-Toranzo
  2. Julieta G Hamze
  3. Enrica Bianchi
  4. Beatriz Fernández-Fuertes
  5. Serafín Pérez-Cerezales
  6. Ricardo Laguna-Barraza
  7. Raúl Fernández-González
  8. Pat Lonergan
  9. Alfonso Gutiérrez-Adán
  10. Gavin J Wright
  11. María Jiménez-Movilla
  12. Pablo Bermejo-Álvarez
(2020)
TMEM95 is a sperm membrane protein essential for mammalian fertilization
eLife 9:e53913.
https://doi.org/10.7554/eLife.53913

Share this article

https://doi.org/10.7554/eLife.53913

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