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HIPK4 is essential for murine spermiogenesis

Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are not well understood, and we demonstrate here that homeodomain-interacting protein kinase 4 (HIPK4) is...

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Autores principales: Crapster, J Aaron, Rack, Paul G, Hellmann, Zane J, Le, Austen D, Adams, Christopher M, Leib, Ryan D, Elias, Joshua E, Perrino, John, Behr, Barry, Li, Yanfeng, Lin, Jennifer, Zeng, Hong, Chen, James K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067585/
https://www.ncbi.nlm.nih.gov/pubmed/32163033
http://dx.doi.org/10.7554/eLife.50209
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author Crapster, J Aaron
Rack, Paul G
Hellmann, Zane J
Le, Austen D
Adams, Christopher M
Leib, Ryan D
Elias, Joshua E
Perrino, John
Behr, Barry
Li, Yanfeng
Lin, Jennifer
Zeng, Hong
Chen, James K
author_facet Crapster, J Aaron
Rack, Paul G
Hellmann, Zane J
Le, Austen D
Adams, Christopher M
Leib, Ryan D
Elias, Joshua E
Perrino, John
Behr, Barry
Li, Yanfeng
Lin, Jennifer
Zeng, Hong
Chen, James K
author_sort Crapster, J Aaron
collection PubMed
description Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are not well understood, and we demonstrate here that homeodomain-interacting protein kinase 4 (HIPK4) is essential for spermiogenesis and male fertility in mice. HIPK4 is predominantly expressed in round and early elongating spermatids, and Hipk4 knockout males are sterile, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Hipk4 mutant sperm have reduced oocyte binding and are incompetent for in vitro fertilization, but they can still produce viable offspring via intracytoplasmic sperm injection. Optical and electron microscopy of HIPK4-null male germ cells reveals defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongation and abnormal head morphologies in mature spermatozoa. We further observe that HIPK4 overexpression induces branched F-actin structures in cultured fibroblasts and that HIPK4 deficiency alters the subcellular distribution of an F-actin capping protein in the testis, supporting a role for this kinase in cytoskeleton remodeling. Our findings establish HIPK4 as an essential regulator of sperm head shaping and potential target for male contraception.
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spelling pubmed-70675852020-03-18 HIPK4 is essential for murine spermiogenesis Crapster, J Aaron Rack, Paul G Hellmann, Zane J Le, Austen D Adams, Christopher M Leib, Ryan D Elias, Joshua E Perrino, John Behr, Barry Li, Yanfeng Lin, Jennifer Zeng, Hong Chen, James K eLife Cell Biology Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are not well understood, and we demonstrate here that homeodomain-interacting protein kinase 4 (HIPK4) is essential for spermiogenesis and male fertility in mice. HIPK4 is predominantly expressed in round and early elongating spermatids, and Hipk4 knockout males are sterile, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Hipk4 mutant sperm have reduced oocyte binding and are incompetent for in vitro fertilization, but they can still produce viable offspring via intracytoplasmic sperm injection. Optical and electron microscopy of HIPK4-null male germ cells reveals defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongation and abnormal head morphologies in mature spermatozoa. We further observe that HIPK4 overexpression induces branched F-actin structures in cultured fibroblasts and that HIPK4 deficiency alters the subcellular distribution of an F-actin capping protein in the testis, supporting a role for this kinase in cytoskeleton remodeling. Our findings establish HIPK4 as an essential regulator of sperm head shaping and potential target for male contraception. eLife Sciences Publications, Ltd 2020-03-12 /pmc/articles/PMC7067585/ /pubmed/32163033 http://dx.doi.org/10.7554/eLife.50209 Text en © 2020, Crapster et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Crapster, J Aaron
Rack, Paul G
Hellmann, Zane J
Le, Austen D
Adams, Christopher M
Leib, Ryan D
Elias, Joshua E
Perrino, John
Behr, Barry
Li, Yanfeng
Lin, Jennifer
Zeng, Hong
Chen, James K
HIPK4 is essential for murine spermiogenesis
title HIPK4 is essential for murine spermiogenesis
title_full HIPK4 is essential for murine spermiogenesis
title_fullStr HIPK4 is essential for murine spermiogenesis
title_full_unstemmed HIPK4 is essential for murine spermiogenesis
title_short HIPK4 is essential for murine spermiogenesis
title_sort hipk4 is essential for murine spermiogenesis
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067585/
https://www.ncbi.nlm.nih.gov/pubmed/32163033
http://dx.doi.org/10.7554/eLife.50209
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