Image of the month - TRIM73 unveiled in ovary

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mIHC/IF image showing TRIM73 protein localization (green) in granulosa cells (cyan) in ovary. Red marks follicle cell cytoplasm, white follicle cell nucleus, yellow zona pellucida, magenta endothelial and stromal cells, and blue a nuclear marker.

Tripartite motif-containing protein 73 (gene: TRIM73) is a protein whose expression at the protein level was unveiled only recently by a team affiliated with the Human Protein Atlas. Multiplex immunohistochemistry allowed them to confirm its cell-type specific localization in the ovary, thus significantly advancing our understanding of both TRIM73 and the ovary proteome.

While transcriptomic and functional studies in cell cultures have suggested TRIM37's involvement in protein ubiquitination, its function in normal human tissues remains poorly characterized. Categorized as a missing protein by the neXtProt resource due to the lack of experimental evidence at the protein level, TRIM73's role has remained enigmatic.

However, two recent studies by Méar et al (1,2) have shed light on this mystery by revealing protein expression of several missing proteins, including TRIM37, in the human ovary. Not only have they identified this protein in normal human tissue for the first time, but they have also confirmed, through multiplex immunohistochemistry (mIHC/IF) analysis, that TRIM37 (green) localizes to cells labeled as granulosa cells (cyan) in ovarian follicles. This finding is further validated by single-cell RNA sequencing data, which shows elevated expression in granulosa cells, among a few other cell types.

These two studies underscore the power of spatial proteomics combined with transcriptomics in identifying and validating missing proteins in organs with insufficiently characterized proteomes, such as the ovary. It is hoped that future endeavors will continue to uncover the complexities of ovarian biology and enhance our understanding of female reproductive health.

For more details about the mIHC/IF technique visit our method page, and Human Protein Atlas single-cell RNA sequencing data is available here.

1. Méar et al., Transcriptomics and Spatial Proteomics for Discovery and Validation of Missing Proteins in the Human Ovary. J Proteome Res (2024)

2. Méar et al., Spatial Proteomics for Further Exploration of Missing Proteins: A Case Study of the Ovary. J Proteome Res (2023)