Cyclophilin A Isomerisation of Septin 2 Mediates Abscission during Cytokinesis

• Published in: International journal of molecular sciences Vol. 24; no. 13; p. 11084
• Main Authors: Gorry, Rebecca L, Brennan, Kieran, Lavin, Paul T M, Mazurski, Tayler, Mary, Charline, Matallanas, David, Guichou, Jean-François, Mc Gee, Margaret M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.07.2023; MDPI
• Subjects: Abscission; Amino acids; Cancer; Cell cycle; Cell Division; Cells; cyclophilin; Cyclophilin A - genetics; Cyclophilin A - metabolism; Cytokinesis; Cytokinesis - genetics; Genotype & phenotype; GTP-binding protein; HeLa Cells; Humans; Isomerization; Life Sciences; Localization; Phenotypes; Proline; prolyl isomerase; Protein binding; Proteins; Septin; Septins - genetics; Septins - metabolism; Signal transduction; Yeast; cell division; prolyl isomerase; cancer; cyclophilin; cytokinesis; cyclophilin prolyl isomerase cytokinesis cell division cancer
• ISSN: 1422-0067; 1661-6596; 1422-0067; 1661-6596
• DOI: 10.3390/ijms241311084

The isomerase activity of Cyclophilin A is important for midbody abscission during cell division, however, to date, midbody substrates remain unknown. In this study, we report that the GTP-binding protein Septin 2 interacts with Cyclophilin A. We highlight a dynamic series of Septin 2 phenotypes at the midbody, previously undescribed in human cells. Furthermore, Cyclophilin A depletion or loss of isomerase activity is sufficient to induce phenotypic Septin 2 defects at the midbody. Structural and molecular analysis reveals that Septin 2 proline 259 is important for interaction with Cyclophilin A. Moreover, an isomerisation-deficient EGFP-Septin 2 proline 259 mutant displays defective midbody localisation and undergoes impaired abscission, which is consistent with data from cells with loss of Cyclophilin A expression or activity. Collectively, these data reveal Septin 2 as a novel interacting partner and isomerase substrate of Cyclophilin A at the midbody that is required for abscission during cytokinesis in cancer cells.