Sfi1-KO Mouse

Sfi1 is a centrin-binding protein conserved from yeast to humans. In yeast, it is essential for the duplication of the spindle pole body (SPB), the functional equivalent of the mammalian centrosome [3,4,5]. In mammals, it has been implicated in centriole-related processes, which are crucial for brain development and ciliogenesis [1,2].

In human cells, depletion of SFI1 results in the loss of the distal pool of Centrin, affecting centriolar architecture, CEP164 distribution, and CP110 removal during ciliogenesis, without altering centriole duplication [1]. In mammalian cells, SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL, and USP9X-mediated deubiquitylation protects STIL from degradation [2]. In fission yeast, mutations in Sfi1, like the Trp-to-Arg mutant (sfi1-M46), lead to monopolar spindles and mitosis and cytokinesis defects, as Sfi1-M46 protein associates preferentially with one of the two daughter SPBs, resulting in a failure of new SPB assembly in the SPB receiving insufficient Sfi1 [5].

In conclusion, Sfi1 is vital for processes related to centrosome/SPB duplication and centriole architecture across different species. In mammals, its role in centriole-related functions has implications for neurodevelopment. Studies on Sfi1, especially through loss-of-function models in yeast and mammalian cells, help in understanding the biological processes underlying cell division, ciliogenesis, and their associated diseases.

References:

1. Laporte, Marine H, Bouhlel, Imène B, Bertiaux, Eloïse, Paoletti, Anne, Hamel, Virginie. 2022. Human SFI1 and Centrin form a complex critical for centriole architecture and ciliogenesis. In The EMBO journal, 41, e112107. doi:10.15252/embj.2022112107. https://pubmed.ncbi.nlm.nih.gov/36125182/

2. Kodani, Andrew, Moyer, Tyler, Chen, Allen, Walsh, Christopher A, Reiter, Jeremy F. 2019. SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL. In The Journal of cell biology, 218, 2185-2197. doi:10.1083/jcb.201803041. https://pubmed.ncbi.nlm.nih.gov/31197030/

3. Rüthnick, Diana, Vitale, Jlenia, Neuner, Annett, Schiebel, Elmar. . The N-terminus of Sfi1 and yeast centrin Cdc31 provide the assembly site for a new spindle pole body. In The Journal of cell biology, 220, . doi:10.1083/jcb.202004196. https://pubmed.ncbi.nlm.nih.gov/33523111/

4. Rüthnick, Diana, Schiebel, Elmar. 2016. Duplication of the Yeast Spindle Pole Body Once per Cell Cycle. In Molecular and cellular biology, 36, 1324-31. doi:10.1128/MCB.00048-16. https://pubmed.ncbi.nlm.nih.gov/26951196/

5. Lee, I-Ju, Wang, Ning, Hu, Wen, Du, Li-Lin, Wu, Jian-Qiu. 2014. Regulation of spindle pole body assembly and cytokinesis by the centrin-binding protein Sfi1 in fission yeast. In Molecular biology of the cell, 25, 2735-49. doi:10.1091/mbc.E13-11-0699. https://pubmed.ncbi.nlm.nih.gov/25031431/