Cyclophilin A isomerization of Septin 2 mediates abscission during cytokinesis

ABSTRACT: 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, consistent with data from cells with loss of Cyclophilin A expression or activity. Collectively, this data reveals 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lymphoblastic Leukemia Cell Line, Lymphoblast

DISEASE(S): Myeloid Leukemia

SUBMITTER: Philip Cotter  

LAB HEAD: Margaret M. McGee

PROVIDER: PXD042822 | Pride | 2023-10-24

REPOSITORIES: Pride