Testis specific serine/threonine protein kinase 4 (TSSK4) leads to cell apoptosis relying on its kinase activity

Xiao-Li Wang1,2, You-Heng Wei3, Guo-Long Fu1

  • 1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, China.

Insights

Testis specific serine/threonine protein kinase 4 (TSSK4) induces apoptosis in cells, impacting spermatogenesis. Its kinase activity is crucial for this function, affecting testes weight and germ cell apoptosis in mice.

Area of Science:

  • Reproductive Biology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Testis specific serine/threonine protein kinase 4 (TSSK4) is part of the TSSK family, vital for male reproductive processes.
  • While its kinase activity via autophosphorylation is known, the precise biological role of TSSK4 remains unclear.

Purpose of the Study:

  • To investigate the function of TSSK4 in apoptosis and its implications for spermatogenesis.
  • To determine if TSSK4's kinase activity is essential for its apoptotic function.

Main Methods:

  • Overexpression of GFP-TSSK4 in HeLa cells to observe cellular changes.
  • Flow cytometry analysis of apoptosis induction in various cell lines (HeLa, Cos-7, H1299) using wild-type and kinase-dead TSSK4 mutants.
  • TUNEL technology assessment of apoptosis in spermatogonia and spermatocytes of TSSK4 knockout mice.

Main Results:

  • Overexpression of TSSK4 led to the formation of apoptotic bodies in HeLa cells.
  • TSSK4 induced apoptosis across multiple cell lines, a function dependent on its kinase activity (TSSK4-K54M mutant did not induce apoptosis).
  • TSSK4 knockout mice exhibited increased testes weight and reduced apoptosis in spermatogonia and spermatocytes at postnatal day 21.

Conclusions:

  • TSSK4 induces apoptosis in a kinase activity-dependent manner.
  • TSSK4 plays a role in regulating germ cell apoptosis during spermatogenesis.
  • Dysregulation of TSSK4 function can lead to abnormal testes weight and affect the process of spermatogenesis.

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