Cyclophilin A Isomerisation of Septin 2 Mediates Abscission during Cytokinesis.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
04 Jul 2023
Historique:
received: 15 05 2023
revised: 21 06 2023
accepted: 24 06 2023
medline: 17 7 2023
pubmed: 14 7 2023
entrez: 14 7 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37446263
pii: ijms241311084
doi: 10.3390/ijms241311084
pmc: PMC10341793
pii:
doi:

Substances chimiques

Septins EC 3.6.1.-
Cyclophilin A EC 5.2.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Science Foundation Ireland
ID : 11/RFP.1/CAN/3202
Pays : Ireland

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Auteurs

Rebecca L Gorry (RL)

School of Biomolecular and Biomedical Science (SBBS), Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

Kieran Brennan (K)

School of Biomolecular and Biomedical Science (SBBS), Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

Paul T M Lavin (PTM)

School of Biomolecular and Biomedical Science (SBBS), Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

Tayler Mazurski (T)

School of Biomolecular and Biomedical Science (SBBS), Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

Charline Mary (C)

Centre de Biologie Structurale, CNRS, INSERM, University Montpellier, 34090 Montpellier, France.

David Matallanas (D)

Systems Biology Ireland (SBI), School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland.

Jean-François Guichou (JF)

Centre de Biologie Structurale, CNRS, INSERM, University Montpellier, 34090 Montpellier, France.

Margaret M Mc Gee (MM)

School of Biomolecular and Biomedical Science (SBBS), Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

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