HIPK4 is essential for murine spermiogenesis
| Autor: | Barry Behr, Ryan D. Leib, Austen D Le, Jennifer Lin, John Perrino, Paul G. Rack, Hong Zeng, James K. Chen, Christopher M. Adams, Yanfeng Li, Joshua E. Elias, Zane J Hellmann, J. Aaron Crapster |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Mouse Spermiogenesis medicine.medical_treatment Fluorescent Antibody Technique Intracytoplasmic sperm injection Mice 0302 clinical medicine Biology (General) Cytoskeleton Mice Knockout fertility 0303 health sciences General Neuroscience Gene Expression Regulation Developmental cytoskeleton General Medicine Spermatids Spermatozoa Cell biology Phenotype medicine.anatomical_structure Medicine Acrosome Protein Binding Signal Transduction Research Article endocrine system kinase QH301-705.5 Science HIPK4 Protein Serine-Threonine Kinases Biology Models Biological Filamentous actin General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Spermatogenesis Protein kinase A 030304 developmental biology General Immunology and Microbiology Spermatid urogenital system Cell Biology Oocyte Sperm Actins spermiogenesis Mutation 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | eLife, Vol 9 (2020) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.50209 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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