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Recording Electrical Currents across the Plasma Membrane of Mammalian Sperm Cells
Published on: February 14, 2021
Tssk4 is essential for maintaining the structural integrity of sperm flagellum
Xiaoli Wang1, Youheng Wei2, Guolong Fu3
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, P.R. China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
Abstract:
Tssk4 belongs to the Testis Specific Serine/threonine protein Kinase (TSSK) family, members of which play an important role in spermatogenesis and/or spermiogenesis. Several Tssk family proteins have extensively been studied. However, the exact function of Tssk4 remains unclear. A Tssk4 knockout mouse model was generated and the males were subfertile due to seriously decreased sperm motility. The ultrastructure of the Tssk4(-/-)sperm tail is disorganized at the midpiece-principal piece junction, leading to a severe bend in the sperm flagellum. One or more axonemal microtubule doublets are absent and the midpiece is fused with the principal piece. Furthermore, we identified the association between Tssk4 and Odf2, a prominent cytoskeletal protein of the outer dense fiber (ODF) in sperm flagellum. Tssk4 can change the phosphorylation state of Odf2 and conversely Odf2 potentiates the autophosphorylation activity of Tssk4. These findings reveal that Tssk4 is required for maintaining the structural integrity of sperm flagellum and male fertility.
Insights
Testis Specific Serine/threonine protein Kinase 4 (Tssk4) is crucial for sperm structure and motility. Its absence impairs sperm flagellum integrity, leading to male subfertility.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Spermatogenesis Research
Background:
- The Testis Specific Serine/threonine protein Kinase (TSSK) family is vital for male reproductive processes.
- While many TSSK members are studied, the specific role of Tssk4 in spermatogenesis remains largely unknown.
Purpose of the Study:
- To elucidate the function of Tssk4 in sperm development and male fertility.
- To investigate the structural and molecular consequences of Tssk4 deficiency.
Main Methods:
- Generation and analysis of a Tssk4 knockout mouse model.
- Examination of sperm ultrastructure and motility.
- Investigation of Tssk4 interactions with other sperm proteins, specifically Odf2.
Main Results:
- Tssk4 knockout male mice exhibited subfertility with significantly reduced sperm motility.
- Sperm flagella in Tssk4(-/-) mice showed disorganized ultrastructure, particularly at the midpiece-principal piece junction, with absent microtubule doublets and fused segments.
- Tssk4 was found to associate with Odf2, influencing its phosphorylation state and vice versa, suggesting a functional interplay.
Conclusions:
- Tssk4 is essential for maintaining the structural integrity of the sperm flagellum.
- Tssk4 plays a critical role in ensuring normal sperm motility and overall male fertility.
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