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
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: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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