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.
Department of Cellular and Developmental Biology, School of Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Glenn C
GC
Simon
Eric
E
Schonteich
Christine C
CC
Wu
Alisa
A
Piekny
Damian
D
Ekiert
Xinzi
X
Yu
Gwyn W
GW
Gould
Michael
M
Glotzer
Rytis
R
Prekeris
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