The armadillo protein p0071 regulates Rho signalling during cytokinesis.
Cytokinesis requires the spatio-temporal coordination of cell-cycle control and cytoskeletal reorganization. Members of the Rho-family of GTPases are crucial regulators of this process and assembly of the contractile ring depends on local activation of Rho signalling. Here, we show that the armadillo protein p0071, unlike its relative p120(ctn), is localized at the midbody during cytokinesis and is essential for cell division. Both knockdown and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinucleated cells and induction of apoptosis. This failure of cytokinesis seemingly correlated with the deregulation of Rho activity in response to altered p0071 expression. The function of p0071 in regulating Rho activity occurred through an association of p0071 with RhoA, as well as the physical and functional interaction of p0071 with Ect2, the one Rho guanine-nucleotide exchange factor (GEF) essential for cytokinesis. These findings support an essential role for p0071 in spatially regulating restricted Rho signalling during cytokinesis.
Wolf
Annika
A
Institute for Pathophysiology, Division of Pathobiochemistry, Martin-Luther-University Halle, Hollystrasse 1, 06114 Halle, Germany.
Keil
Rene
R
Götzl
Oliver
O
Mun
Andrej
A
Schwarze
Katrin
K
Lederer
Marcell
M
Hüttelmaier
Stefan
S
Hatzfeld
Mechthild
M
D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D051191:Plakophilins / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D051186:Armadillo Domain Proteins; C489850:ECT2 protein, human; C105677:PKP4 protein, human; D051191:Plakophilins; D011518:Proto-Oncogene Proteins; D020742:rhoA GTP-Binding Protein