Tmprss13, also known as mosaic serine protease large-form (MSPL), is a member of the type II transmembrane serine protease (TTSP) family. It has trypsin-like catalytic activity and is involved in multiple biological processes. It plays a role in proteolytic processing of various molecules such as prohormones and growth factor precursors, and is also implicated in the pathogenicity of many viruses and bacteria [5].

In mice with Tmprss13 gene disrupted by a β-galactosidase-neomycin fusion gene insertion, abnormal skin development was observed, leading to compromised epidermal barrier function as measured by transepidermal fluid loss rate in newborn mice. This indicates its importance in stratum corneum formation [7]. In addition, in colorectal cancer cell lines, Tmprss13 silencing increased apoptosis and impaired invasive potential, while overexpression increased tolerance to apoptosis-inducing agents, suggesting its role in cancer cell survival and drug-resistance [4]. Regarding viral infections, Tmprss13 significantly facilitates the cell entry of swine acute diarrhea syndrome coronavirus (SADS-CoV), and also enhances the cell-cell membrane fusion and cleavage of its spike protein. Both human and pig Tmprss13 have this effect, and its action at the entry step is sensitive to serine protease inhibitor Camostat [1]. Tmprss13 can also cleave the spike protein of SARS-CoV-2 and allow its pseudotyped virus entry into cells. Exogenous expression of Tmprss13 enhanced cellular uptake and replication of SARS-CoV-2, and it was shown to have different preferences for residues in the S2' cleavage motif of the SARS-CoV-2 spike compared to TMPRSS2 [2,3,6].

In conclusion, Tmprss13 is crucial for epidermal barrier formation during skin development. In disease contexts, it promotes cancer cell survival and drug-resistance in colorectal cancer. It also significantly impacts the cell entry of certain coronaviruses, including SADS-CoV and SARS-CoV-2. Studies using gene-knockout mouse models have been instrumental in revealing these functions, providing insights into potential therapeutic targets for skin-related disorders, cancer, and viral infections.

References:

1. Han, Yutong, Ma, Yanlong, Wang, Ziqiao, Ye, Rong, Zhang, Rong. . TMPRSS13 promotes the cell entry of swine acute diarrhea syndrome coronavirus. In Journal of medical virology, 96, e29712. doi:10.1002/jmv.29712. https://pubmed.ncbi.nlm.nih.gov/38808555/

2. Gatineau, Jérôme, Nidercorne, Charlotte, Dupont, Aurélie, Niedergang, Florence, Castellano, Flavia. 2022. IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike. In Frontiers in immunology, 13, 982839. doi:10.3389/fimmu.2022.982839. https://pubmed.ncbi.nlm.nih.gov/36131918/

3. Kishimoto, Mai, Uemura, Kentaro, Sanaki, Takao, Sawa, Hirofumi, Sasaki, Michihito. 2021. TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein. In Viruses, 13, . doi:10.3390/v13030384. https://pubmed.ncbi.nlm.nih.gov/33671076/

4. Varela, Fausto A, Foust, Victoria L, Hyland, Thomas E, Todi, Sokol V, List, Karin. 2020. TMPRSS13 promotes cell survival, invasion, and resistance to drug-induced apoptosis in colorectal cancer. In Scientific reports, 10, 13896. doi:10.1038/s41598-020-70636-4. https://pubmed.ncbi.nlm.nih.gov/32807808/

5. Kido, Hiroshi, Okumura, Yuushi. 2008. MSPL/TMPRSS13. In Frontiers in bioscience : a journal and virtual library, 13, 754-8. doi:. https://pubmed.ncbi.nlm.nih.gov/17981585/

6. Stevaert, Annelies, Van Berwaer, Ria, Mestdagh, Cato, Laporte, Manon, Naesens, Lieve. 2022. Impact of SARS-CoV-2 Spike Mutations on Its Activation by TMPRSS2 and the Alternative TMPRSS13 Protease. In mBio, 13, e0137622. doi:10.1128/mbio.01376-22. https://pubmed.ncbi.nlm.nih.gov/35913162/

7. Madsen, Daniel H, Szabo, Roman, Molinolo, Alfredo A, Bugge, Thomas H. . TMPRSS13 deficiency impairs stratum corneum formation and epidermal barrier acquisition. In The Biochemical journal, 461, 487-95. doi:10.1042/BJ20140337. https://pubmed.ncbi.nlm.nih.gov/24832573/