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TAp73 is essential for germ cell adhesion and maturation in testis

A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis...

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Autores principales: Holembowski, Lena, Kramer, Daniela, Riedel, Dietmar, Sordella, Raffaella, Nemajerova, Alice, Dobbelstein, Matthias, Moll, Ute M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971741/
https://www.ncbi.nlm.nih.gov/pubmed/24662569
http://dx.doi.org/10.1083/jcb.201306066
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author Holembowski, Lena
Kramer, Daniela
Riedel, Dietmar
Sordella, Raffaella
Nemajerova, Alice
Dobbelstein, Matthias
Moll, Ute M.
author_facet Holembowski, Lena
Kramer, Daniela
Riedel, Dietmar
Sordella, Raffaella
Nemajerova, Alice
Dobbelstein, Matthias
Moll, Ute M.
author_sort Holembowski, Lena
collection PubMed
description A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73 knockout (TAp73KO) and p73KO mice, but not ΔNp73KO mice, display a “near-empty seminiferous tubule” phenotype due to massive premature loss of immature germ cells. The cellular basis of this phenotype is defective cell–cell adhesions of developing germ cells to Sertoli nurse cells, with likely secondary degeneration of Sertoli cells, including the blood–testis barrier, which leads to disruption of the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, which is produced in germ cells, controls a coordinated transcriptional program of adhesion- and migration-related proteins including peptidase inhibitors, proteases, receptors, and integrins required for germ–Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose the testis as a unique organ with strict division of labor among all family members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures fertility by enabling sperm maturation.
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spelling pubmed-39717412014-10-01 TAp73 is essential for germ cell adhesion and maturation in testis Holembowski, Lena Kramer, Daniela Riedel, Dietmar Sordella, Raffaella Nemajerova, Alice Dobbelstein, Matthias Moll, Ute M. J Cell Biol Research Articles A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73 knockout (TAp73KO) and p73KO mice, but not ΔNp73KO mice, display a “near-empty seminiferous tubule” phenotype due to massive premature loss of immature germ cells. The cellular basis of this phenotype is defective cell–cell adhesions of developing germ cells to Sertoli nurse cells, with likely secondary degeneration of Sertoli cells, including the blood–testis barrier, which leads to disruption of the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, which is produced in germ cells, controls a coordinated transcriptional program of adhesion- and migration-related proteins including peptidase inhibitors, proteases, receptors, and integrins required for germ–Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose the testis as a unique organ with strict division of labor among all family members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures fertility by enabling sperm maturation. The Rockefeller University Press 2014-03-31 /pmc/articles/PMC3971741/ /pubmed/24662569 http://dx.doi.org/10.1083/jcb.201306066 Text en © 2014 Holembowski et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Holembowski, Lena
Kramer, Daniela
Riedel, Dietmar
Sordella, Raffaella
Nemajerova, Alice
Dobbelstein, Matthias
Moll, Ute M.
TAp73 is essential for germ cell adhesion and maturation in testis
title TAp73 is essential for germ cell adhesion and maturation in testis
title_full TAp73 is essential for germ cell adhesion and maturation in testis
title_fullStr TAp73 is essential for germ cell adhesion and maturation in testis
title_full_unstemmed TAp73 is essential for germ cell adhesion and maturation in testis
title_short TAp73 is essential for germ cell adhesion and maturation in testis
title_sort tap73 is essential for germ cell adhesion and maturation in testis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971741/
https://www.ncbi.nlm.nih.gov/pubmed/24662569
http://dx.doi.org/10.1083/jcb.201306066
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