Capping protein regulates actin dynamics during cytokinetic midbody maturation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 9; pp. 2138 - 2143
• Main Authors: Terry, Stephen J., Donà, Federico, Osenberg, Paul, Carlton, Jeremy G., Eggert, Ulrike S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.02.2018
• Subjects: Abscission; Actin; Actin Capping Proteins - physiology; Actin Cytoskeleton - physiology; Actins; Actomyosin; Assembly; Biological Sciences; Capping; Cell cycle; Cell division; Cell Membrane; Contractility; Contraction; Cytokinesis; Cytokinesis - physiology; Cytoskeleton; Dismantling; Endosomal Sorting Complexes Required for Transport - metabolism; Epithelial Cells - physiology; Epithelium, Corneal - cytology; Eukaryotes; Fetal Proteins - genetics; Fetal Proteins - metabolism; Filaments; Formins; Gene Expression Regulation - physiology; HeLa Cells; Humans; Machinery and equipment; Maturation; Microfilament Proteins; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Polymerization; Proteins; Regulators; midbody; capping protein; F-actin; formins; cytokinesis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1722281115

During cytokinesis, a cleavage furrow generated by actomyosin ring contraction is restructured into the midbody, a platform for the assembly of the abscission machinery that controls the final separation of daughter cells. The polymerization state of F-actin is important during assembly, ingression, disassembly, and closure of the contractile ring and for the cytoskeletal remodeling that accompanies midbody formation and progression to abscission. Actin filaments must be cleared from the abscission sites before the final cut can take place. Although many conserved proteins interact with and influence the polymerization state of actin filaments, it is poorly understood how they regulate cytokinesis in higher eukaryotes. We report here that the actin capping protein (CP), a barbed end actin binding protein, participates in the control of actin polymerization during later stages of cytokinesis in human cells. Cells depleted of CP furrow and form early midbodies, but they fail cytokinesis. Appropriate recruitment of the ESCRT-III abscission machinery to the midbody is impaired, preventing the cell from progressing to the abscission stage. To generate actin filaments of optimal length, different actin nucleators, such as formins, balance CP’s activity. Loss of actin capping activity leads to excessive accumulation of formin-based linear actin filaments. Depletion of the formin FHOD1 results in partial rescue of CP-induced cytokinesis failure, suggesting that it can antagonize CP activity during midbody maturation. Our work suggests that the actin cytoskeleton is remodeled in a stepwise manner during cytokinesis, with different regulators at different stages required for successful progression to abscission.