Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis.
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.
Simon
Glenn C
GC
Department of Cellular and Developmental Biology, School of Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Schonteich
Eric
E
Wu
Christine C
CC
Piekny
Alisa
A
Ekiert
Damian
D
Yu
Xinzi
X
Gould
Gwyn W
GW
Glotzer
Michael
M
Prekeris
Rytis
R
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002455:Cell Division; D048749:Cytokinesis; D011992:Endosomes / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000199:Actins; D020690:GTPase-Activating Proteins; D051550:I-kappa B Kinase; D011518:Proto-Oncogene Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C489850:ECT2 protein, human; C491731:IKBKG protein, human; C115995:mgcRacGAP