TDRD7 participates in lens development and spermiogenesis by mediating autophagosome maturation

Chaofeng Tu1,2,3, Haiyu Li1, Xuyang Liu4

  • 1Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Autophagy
|February 23, 2021
PubMed

Insights

Tudor domain containing 7 (TDRD7) is crucial for autophagosome maturation, essential for eye and testicular development. Its depletion causes cataracts and infertility by disrupting autophagy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Mutations in TDRD7 (tudor domain containing 7) cause a human syndrome with congenital cataracts (CCs) and non-obstructive azoospermia (NOA).
  • The precise molecular mechanisms of TDRD7 in ocular and testicular development remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular function of TDRD7 in autophagy.
  • To elucidate the role of TDRD7 in lens and sperm development.

Main Methods:

  • Depletion of TDRD7 in mouse embryonic fibroblasts (MEFs) and analysis of autophagic flux.
  • Transcriptome analysis and biochemical assays to identify TDRD7 interacting partners and targets.
  • Assessment of lens and testicular phenotypes in TDRD7-deficient mice.

Main Results:

  • TDRD7 depletion leads to autophagosome accumulation and impaired autophagic flux due to failed autophagosome-lysosome fusion.
  • TDRD7 directly binds to TBC1D20 mRNA, downregulating its expression and disrupting autophagosome maturation.
  • TDRD7 deficiency in mice causes congenital cataracts and defects in spermiogenesis, mirroring human disease phenotypes.

Conclusions:

  • TDRD7 is essential for autophagosome maturation, regulating lens transparency and sperm development.
  • Disrupted autophagy due to TDRD7 dysfunction is implicated as a key mechanism underlying congenital cataracts and non-obstructive azoospermia.

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