MgcRacGAP and RhoA colocalize at the midbody during cytokinesis.


We already knew the players—MgcRacGAP, Aurora B, and RhoA—and that knocking out any one of them caused failure of cytokinesis; but it wasn't clear how they were connected. Now, it appears that Aurora B phosphorylates the GAP domain of MgcRacGAP, allowing it to turn its GAP activity toward RhoA, according to data from Yukinori Minoshima, Toshiyuki Kawashima, Toshio Kitamura (University of Tokyo, Tokyo, Japan), and colleagues.

When they first isolated MgcRacGAP, the group found that most of its activity was directed toward Rac1 and Cdc42, but there were hints—although inconsistent ones—that it also had activity toward Rho proteins. In the new work, Kitamura and colleagues found that, late in mitosis, Aurora B, RhoA, and MgcRacGAP congregate at the midbody, where Aurora B phosphorylates a serine in the GAP domain of MgcRacGAP. The phosphorylated GAP protein then stimulates the GTPase activity of RhoA, converting GTP-bound active RhoA to GDP-bound inactive RhoA, and promotes the completion of cytokinesis and cell division. Overexpression of a phosphorylation-deficient mutant of MgcRacGAP blocks RhoA activity and results in polyploid cells.

“This is the first demonstration that a modification of a GAP changes its target specificity,” says Kitamura. “Biologically the interesting thing is that in the beginning of cell division MgcRacGAP probably works through Rac1 and Cdc42, which function in mitotic spindle formation. Then during the late stage of cell division and cytokinesis, MgcRacGAP converts itself to a RhoGAP and exerts itself through RhoA.” ▪


Minoshima, Y., et al.
Dev. Cell.