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    Pathoproteomics of testicular tissue deficient in the GARP component VPS54: The wobbler mouse model of globozoospermia


    Jockusch, Harald and Holland, Ashling and Staunton, Lisa and Schmitt-John, Thomas and Heimann, Peter and Dowling, Paul and Ohlendieck, Kay (2014) Pathoproteomics of testicular tissue deficient in the GARP component VPS54: The wobbler mouse model of globozoospermia. Proteomics, 14 (7-8). pp. 839-852. ISSN 1615-9853

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    Abstract

    In human globozoospermia, round-headed spermatozoa lack an acrosome and therefore cannot properly interact with oocytes. In the wobbler (WR) mouse, an L967Q missense mutation in the vesicular protein-sorting factor VPS54 causes motor neuron degeneration and globozoospermia. Although electron microscopy of WR testis shows all major components of spermatogenesis, they appear in a deranged morphology that prevents the formation of the acrosome. In order to determine proteome-wide changes, affected testes were analysed by 2D-DIGE and MS. The concentration of 8 proteins was increased and that of 35 proteins decreased as compared to wild type. Mass spectrometric analysis identified proteins with an altered concentration to be associated with metabolite transport, fatty acid metabolism, cellular interactions, microtubule assembly and stress response (chaperones Hsp70–2 and Hsp90α). Minor changes were observed for proteins involved in cell redox homeostasis, cytoskeleton formation, PTMs, detoxification and metabolism. The most dramatically decreased protein in WR testis was identified as fatty acid binding protein FABP3, as confirmed by immunoblot analysis. We conclude that a missense mutation in VPS54, an essential component of the Golgi-associated retrograde protein complex, not only prevents the formation of an acrosome but also initiates a cascade of metabolic abnormalities and a stress reaction.

    Item Type: Article
    Additional Information: The definitive published version of this article is available at DOI: 10.1002/pmic.201300189
    Keywords: Acrosome; Animal proteomics; Fatty acid binding protein; GARP complex; HSP; Spermatogenesis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 6929
    Identification Number: https://doi.org/10.1002/pmic.201300189
    Depositing User: Paul Dowling
    Date Deposited: 28 Jan 2016 15:18
    Journal or Publication Title: Proteomics
    Publisher: Wiley
    Refereed: Yes
    Funders: Health Research Board (HRB), Higher Education Authority (HEA), Fonds der Chemischen Industrie
    URI:

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