Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis

• Published in: The EMBO journal Vol. 27; no. 13; pp. 1791 - 1803
• Main Authors: Simon, Glenn C, Schonteich, Eric, Wu, Christine C, Piekny, Alisa, Ekiert, Damian, Yu, Xinzi, Gould, Gwyn W, Glotzer, Michael, Prekeris, Rytis
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 09-07-2008; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Abscission; Actins - metabolism; ADP-Ribosylation Factors - metabolism; Binding sites; Cell Division; Cellular biology; Cyk-4; Cytokinesis; EMBO06; EMBO20; endosomes; Endosomes - metabolism; FIP3; Furrows; GTPase-Activating Proteins - metabolism; HeLa Cells; Humans; I-kappa B Kinase - metabolism; Molecular biology; Proteins; Proto-Oncogene Proteins - metabolism; rab GTP-Binding Proteins - metabolism; Rab11; endosomes; Rab11; Cyk‐4; cytokinesis; FIP3
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2008.112

Cytokinesis is a highly regulated and dynamic event that involves the reorganization of the cytoskeleton and membrane compartments. Recently, FIP3 has been implicated in targeting of recycling endosomes to the mid‐body of dividing cells and is found required for abscission. Here, we demonstrate that the centralspindlin component Cyk‐4 is a FIP3‐binding protein. Furthermore, we show that FIP3 binds to Cyk‐4 at late telophase and that centralspindlin may be required for FIP3 recruitment to the mid‐body. We have mapped the FIP3‐binding region on Cyk‐4 and show that it overlaps with the ECT2‐binding domain. Finally, we demonstrate that FIP3 and ECT2 form mutually exclusive complexes with Cyk‐4 and that dissociation of ECT2 from the mid‐body at late telophase may be required for the recruitment of FIP3 and recycling endosomes to the cleavage furrow. Thus, we propose that centralspindlin complex not only regulates acto‐myosin ring contraction but also endocytic vesicle transport to the cleavage furrow and it does so through sequential interactions with ECT2 and FIP3.