KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated...

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Autores principales:	Lee B Smith, Laura Milne, Nancy Nelson, Sharon Eddie, Pamela Brown, Nina Atanassova, Moira K O'Bryan, Liza O'Donnell, Danielle Rhodes, Sara Wells, Diane Napper, Patrick Nolan, Zuzanna Lalanne, Michael Cheeseman, Josephine Peters
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/05d4d8773d914772b7862b40f7d997eb
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spelling	oai:doaj.org-article:05d4d8773d914772b7862b40f7d997eb2021-11-18T06:18:33ZKATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.1553-73901553-740410.1371/journal.pgen.1002697https://doaj.org/article/05d4d8773d914772b7862b40f7d997eb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22654668/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.Lee B SmithLaura MilneNancy NelsonSharon EddiePamela BrownNina AtanassovaMoira K O'BryanLiza O'DonnellDanielle RhodesSara WellsDiane NapperPatrick NolanZuzanna LalanneMichael CheesemanJosephine PetersPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 5, p e1002697 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Lee B Smith Laura Milne Nancy Nelson Sharon Eddie Pamela Brown Nina Atanassova Moira K O'Bryan Liza O'Donnell Danielle Rhodes Sara Wells Diane Napper Patrick Nolan Zuzanna Lalanne Michael Cheeseman Josephine Peters KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
description	Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.
format	article
author	Lee B Smith Laura Milne Nancy Nelson Sharon Eddie Pamela Brown Nina Atanassova Moira K O'Bryan Liza O'Donnell Danielle Rhodes Sara Wells Diane Napper Patrick Nolan Zuzanna Lalanne Michael Cheeseman Josephine Peters
author_facet	Lee B Smith Laura Milne Nancy Nelson Sharon Eddie Pamela Brown Nina Atanassova Moira K O'Bryan Liza O'Donnell Danielle Rhodes Sara Wells Diane Napper Patrick Nolan Zuzanna Lalanne Michael Cheeseman Josephine Peters
author_sort	Lee B Smith
title	KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
title_short	KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
title_full	KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
title_fullStr	KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
title_full_unstemmed	KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
title_sort	katnal1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/05d4d8773d914772b7862b40f7d997eb
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KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

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