Final stages of cytokinesis and midbody ring formation are controlled by BRUCE.
Cytokinesis involves the formation of a cleavage furrow, followed by abscission, the cutting of the midbody channel, the final bridge between dividing cells. Recently, the midbody ring became known as central for abscission, but its regulation remains enigmatic. Here, we identify BRUCE, a 528 kDa multifunctional protein, which processes ubiquitin-conjugating activity, as a major regulator of abscission. During cytokinesis, BRUCE moves from the vesicular system to the midbody ring and serves as a platform for the membrane delivery machinery and mitotic regulators. Depletion of BRUCE in cell cultures causes defective abscission and cytokinesis-associated apoptosis, accompanied by a block of vesicular targeting and defective formation of the midbody and the midbody ring. Notably, ubiquitin relocalizes from midbody microtubules to the midbody ring during cytokinesis, and depletion of BRUCE disrupts this process. We propose that BRUCE coordinates multiple steps required for abscission and that ubiquitylation may be a crucial trigger.
Pohl
Christian
C
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Jentsch
Stefan
S
D017209:Apoptosis; D002460:Cell Line; D048749:Cytokinesis; D011992:Endosomes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000378:metabolism*; D007425:Intracellular Membranes / Q000737:chemistry; D025801:Ubiquitin / Q000032:analysis / Q000378:metabolism; D054875:Ubiquitination; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D051034:Inhibitor of Apoptosis Proteins; D025801:Ubiquitin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C401541:BIRC6 protein, human; C082377:RAB8A protein, human