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CCDC189 affects sperm flagellum formation by interacting with CABCOCO1.

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The coiled-coil domain-containing 189 (Ccdc189) gene is crucial for sperm flagellum formation. Its inactivation leads to male infertility due to abnormal sperm flagella, a key cause of multiple morphological abnormalities of the sperm flagella (MMAF).

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Area of Science:

  • Reproductive Biology
  • Molecular Genetics
  • Cell Biology

Background:

  • Multiple morphological abnormalities of the sperm flagella (MMAF) are a significant cause of male infertility.
  • Understanding the genetic and molecular basis of sperm flagellum formation is critical for addressing male infertility.

Purpose of the Study:

  • To investigate the role of the coiled-coil domain-containing 189 (Ccdc189) gene in sperm flagellum formation and male fertility.
  • To identify proteins interacting with CCDC189 and elucidate their function in sperm development.

Main Methods:

  • Gene expression analysis in mouse testes.
  • Phenotypic analysis of sperm from Ccdc189-deficient mice using histology and immunoelectron microscopy.
  • Co-immunoprecipitation and mass spectrometry to identify CCDC189-interacting proteins.
  • Functional studies of Ccdc189 and its interacting partners in sperm development.

Main Results:

  • Ccdc189 is predominantly expressed in mouse testes and its inactivation causes male infertility.
  • Ccdc189-deficient sperm exhibit typical MMAF phenotypes, including coiled, curved, or short flagella.
  • CCDC189 protein localizes to the radial spoke of the sperm axoneme.
  • CABCOCO1 was identified as a CCDC189-interacting protein; its inactivation also results in sperm flagellum malformation.
  • CCDC189 and CABCOCO1 interact with radial spoke protein RSPH1 and intraflagellar transport proteins, and CCDC189 deficiency downregulates CABCOCO1 expression.

Conclusions:

  • Ccdc189 is a radial-spoke-associated protein essential for sperm flagellum formation.
  • The CCDC189-CABCOCO1 complex plays a vital role in maintaining sperm flagellar structure and function.
  • Disruptions in CCDC189-mediated pathways contribute to male infertility associated with MMAF.