Dynamic changes in Rap1 activity are required for cell retraction and spreading during mitosis

• Published in: Journal of cell science Vol. 122; no. 16; pp. 2996 - 3004
• Main Authors: Dao, Vi Thuy, Dupuy, Aurélien Guy, Gavet, Olivier, Caron, Emmanuelle, de Gunzburg, Jean
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15-08-2009; Company of Biologists
• Subjects: Actins - metabolism; Cell Adhesion; Cell Movement; Cell Shape; Cytoskeleton - metabolism; Down-Regulation; Enzyme Activation; HeLa Cells; Humans; Life Sciences; Mitosis; Mutant Proteins - metabolism; rap1 GTP-Binding Proteins - metabolism; Signal Transduction; Integrin; 52 rue des Meuniers; Mitosis; 92220 Bagneux; Rap1; Spreading; Rap1 Mitosis Integrin Spreading Focal adhesion Pérouse Médical 52 rue des Meuniers 92220 Bagneux France; Focal adhesion Pérouse Médical; France
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.041301

At the onset of mitosis, most adherent cells undergo cell retraction characterised by the disassembly of focal adhesions and actin stress fibres. Mitosis takes place in rounded cells, and the two daughter cells spread again after cytokinesis. Because of the well-documented ability of the small GTPase Rap1 to stimulate integrin-dependent adhesion and spreading, we assessed its role during mitosis. We show that Rap1 activity is regulated during this process. Changes in Rap1 activity play an essential role in regulating cell retraction and spreading, respectively, before and after mitosis of HeLa cells. Indeed, endogenous Rap1 is inhibited at the onset of mitosis; conversely, constitutive activation of Rap1 inhibits the disassembly of premitotic focal adhesions and of the actin cytoskeleton, leading to delayed mitosis and to cytokinesis defects. Rap1 activity slowly increases after mitosis ends; inhibition of Rap1 activation by the ectopic expression of the dominant-negative Rap1[S17A] mutant prevents the rounded cells from spreading after mitosis. For the first time, we provide evidence for the direct regulation of adhesion processes during mitosis via the activity of the Rap1 GTPase.