Rab11FIP1 maintains Rab35 at the intercellular bridge to promote actin removal and abscission

J Cell Sci. 2021 Jun 15;134(12):jcs244384. doi: 10.1242/jcs.244384. Epub 2021 Jun 21.

Abstract

Cytokinesis occurs at the end of mitosis/meiosis wherein the cytoplasms of daughter cells are separated. Before abscission, an intercellular bridge containing the remaining furrowing machinery, mitotic spindle and actin cytoskeleton connects the two daughter cells. To remove this actin and allow for the separation of daughter cells, Rab35 vesicles, loaded with the actin oxidizer MICAL1 and the inositol polyphosphate 5-phosphatase OCRL, are recruited to the midbody in a fine-tuned spatiotemporal manner. However, importantly, the means by which these vesicles are recruited is currently unclear. Here, we demonstrate that Rab11FIP1 is recruited to the midbody after Rab35 to scaffold it at the bridge and maintain Rab35 in this region. In the absence of Rab11FIP1, Rab35 dramatically drops from the midbody, inducing defects, such as cytokinetic delays and binucleation due to actin overaccumulation at the intercellular bridge, which can be rescued with Latrunculin A treatment. Importantly, we show that Rab11FIP1 is critical for Rab35 function in actin removal prior to cytokinesis. This article has an associated First Person interview with the first author of the paper.

Keywords: Abscission; Actin; Cytokinesis; Rab11FIP; Rab35; Vesicular trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins* / metabolism
  • Adaptor Proteins, Signal Transducing
  • Cytokinesis*
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Microfilament Proteins / metabolism
  • Mitosis
  • Mixed Function Oxygenases
  • Spindle Apparatus / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Microfilament Proteins
  • RAB11FIP1 protein, human
  • MICAL1 protein, human
  • Mixed Function Oxygenases
  • RAB35 protein, human
  • rab GTP-Binding Proteins

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