HIPK4 is essential for murine spermiogenesis
| Autor: | John Perrino, Hong Zeng, Yanfeng Li, Zane J Hellmann, James K. Chen, Barry Behr, Paul G. Rack, J. Aaron Crapster, Jennifer Lin, Joshua E. Elias |
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| Rok vydání: | 2019 |
| Předmět: |
endocrine system
0303 health sciences Spermatid urogenital system Spermiogenesis medicine.medical_treatment 030302 biochemistry & molecular biology Biology Oocyte Filamentous actin Sperm Intracytoplasmic sperm injection Cell biology 03 medical and health sciences medicine.anatomical_structure medicine Protein kinase A Cytoskeleton reproductive and urinary physiology 030304 developmental biology |
| DOI: | 10.1101/703637 |
| 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. Ultrastructural analyses of HIPK4-null male germ cells reveal 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, 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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