Capping protein regulates actin dynamics during cytokinetic midbody maturation

Stephen J. Terry, Federico Donà, Paul Osenberg, Jeremy G. Carlton, Ulrike S. Eggert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
101 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)2138-2143
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number9
Early online date8 Feb 2018
DOIs
Publication statusPublished - 27 Feb 2018

Keywords

  • Capping protein
  • Cytokinesis
  • F-actin
  • Formins
  • Midbody

Fingerprint

Dive into the research topics of 'Capping protein regulates actin dynamics during cytokinetic midbody maturation'. Together they form a unique fingerprint.

Cite this