Function of the armadillo protein p0071 in Rho signalling

• Applicant: Professorin Dr. Mechthild Hatzfeld
• Subject Area: Cell Biology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40813496

We have recently discovered a surprising new function of the armadillo protein p0071. Unlike its relative p120ctn, p0071 is essential for cell division. Both, knock-down and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinucleated cells and induction of apoptosis. Cytokinesis depends on cytoskeletal reorganisation leading to contractile ring formation. Members of the Rho-family of GTPases are crucial regulators of this process. The failure of cytokinesis in response to altered p0071 expression correlated with the deregulation of Rho-activity. At the midbody, p0071 associated directly with active RhoA as well as with Ect2, the one Rho-guanine nucleotide exchange factor (GEF) essential in cytokinesis. P0071 stimulated RhoA-exchange activity in conjunction with Ect2. Although our findings support an essential role of p0071 in regulating spatially restricted Rho signalling during cytokinesis, its precise function at the contractile ring as well as its function in Rho signalling in other cellular contexts remains elusive. Therefore, we plan to investigate the role of p0071 in the local control of Rho signalling (1) in contractile ring formation during cytokinesis (2) in epithelial cell polarity and epithelial-mesenchymal transition and (3) in neurite outgrowth, retraction and branching.

• DFG Programme: Research Grants