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Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice

 Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpr...

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Autores principales: Kaczmarek, Karina, Studencka, Maja, Meinhardt, Andreas, Wieczerzak, Krzysztof, Thoms, Sven, Engel, Wolfgang, Grzmil, Pawel
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093327/
https://www.ncbi.nlm.nih.gov/pubmed/21460186
http://dx.doi.org/10.1091/mbc.E09-12-0993
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author Kaczmarek, Karina
Studencka, Maja
Meinhardt, Andreas
Wieczerzak, Krzysztof
Thoms, Sven
Engel, Wolfgang
Grzmil, Pawel
author_facet Kaczmarek, Karina
Studencka, Maja
Meinhardt, Andreas
Wieczerzak, Krzysztof
Thoms, Sven
Engel, Wolfgang
Grzmil, Pawel
author_sort Kaczmarek, Karina
collection PubMed
description  Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.
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spelling pubmed-30933272011-07-30 Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice Kaczmarek, Karina Studencka, Maja Meinhardt, Andreas Wieczerzak, Krzysztof Thoms, Sven Engel, Wolfgang Grzmil, Pawel Mol Biol Cell Articles  Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3. The American Society for Cell Biology 2011-05-15 /pmc/articles/PMC3093327/ /pubmed/21460186 http://dx.doi.org/10.1091/mbc.E09-12-0993 Text en © 2011 Kaczmarek et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Kaczmarek, Karina
Studencka, Maja
Meinhardt, Andreas
Wieczerzak, Krzysztof
Thoms, Sven
Engel, Wolfgang
Grzmil, Pawel
Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title_full Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title_fullStr Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title_full_unstemmed Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title_short Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
title_sort overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093327/
https://www.ncbi.nlm.nih.gov/pubmed/21460186
http://dx.doi.org/10.1091/mbc.E09-12-0993
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