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

Abstract

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.

IRGC1, a testis-enriched immunity related GTPase, is important for fibrous sheath integrity and sperm motility in mice

“…The number of pups was counted on the day of birth. For the in vitro fertility assay, in vitro fertilization (IVF) analysis was performed as previously described ( Morohoshi et al., 2021 ) with some minor changes. For ZP-free oocytes, sperm insemination was performed at a final density of 2 ​× ​10 4 spermatozoa/mL.…”

Multi-omic comparisons between CFBE41o- cells stably expressing wild-type CFTR and F508del-mutant CFTR

“…Data in the human protein atlas ( www.proteinatlas.org ) shows expression in human bronchial epithelium but whether it is regulated by CFTR expression per se is unclear. FAM71F1 has mostly been studied in spermatogenesis as it controls acrosome assembly and male fertility [27] which is a phenotype in CFTR deficient patients and whether there is a direct link of CFTR and FAM71F1 in these tissues remains to be determined. C5orf46 is expressed in epithelial cells and has recently been reported to encode an antimicrobial protein with activity against gram negative bacteria [28] .…”

FAM71D is dispensable for spermatogenesis and male fertility in mice

“…FAM71F1 and FAM71F2 are testis specific proteins containing a RAB2B‐binding domain, which is a small GTPase involved in vesicle transport and membrane trafficking. Fam71f1 and Fam71f2 are both essential for proper acrosome formation and normal male fertility (Morohoshi et al, 2021). Our previous research showed that FAM71D, a protein predominantly expressed in the testis, could interact with calmodulin and was involved in sperm motility in vitro (Ma et al, 2017).…”