FAM71F1 binds to RAB2A and RAB2B and is essential for acrosome formation and male fertility in mice

Development. 2021 Nov 1;148(21):dev199644. doi: 10.1242/dev.199644. Epub 2021 Oct 29.


The acrosome is a cap-shaped, Golgi-derived membranous organelle that is located over the anterior of the sperm nucleus and highly conserved throughout evolution. Although morphological changes during acrosome biogenesis in spermatogenesis have been well described, the molecular mechanism underlying this process is still largely unknown. Family with sequence similarity 71, member F1 and F2 (FAM71F1 and FAM71F2) are testis-enriched proteins that contain a RAB2B-binding domain, a small GTPase involved in vesicle transport and membrane trafficking. Here, by generating mutant mice for each gene, we found that Fam71f1 is essential for male fertility. In Fam71f1-mutant mice, the acrosome was abnormally expanded at the round spermatid stage, likely because of enhanced vesicle trafficking. Mass spectrometry analysis after immunoprecipitation indicated that, in testes, FAM71F1 binds not only RAB2B, but also RAB2A. Further study suggested that FAM71F1 binds to the GTP-bound active form of RAB2A/B, but not the inactive form. These results indicate that a complex of FAM71F1 and active RAB2A/B suppresses excessive vesicle trafficking during acrosome formation.

Keywords: Acrosome; Globozoospermia; Mouse; Spermatogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrosome / metabolism*
  • Acrosome / pathology
  • Animals
  • Fertility / physiology*
  • Genetics
  • Golgi Apparatus / metabolism
  • Infertility, Male
  • Male
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Sperm Head / metabolism
  • Spermatogenesis
  • Teratozoospermia / metabolism
  • Testis / metabolism
  • rab GTP-Binding Proteins / metabolism*
  • rab2 GTP-Binding Protein / metabolism*


  • Fam71f1 protein, mouse
  • Nuclear Proteins
  • rab2b protein, mouse
  • Rab2a protein, mouse
  • rab GTP-Binding Proteins
  • rab2 GTP-Binding Protein