Focal adhesion signaling and actin stress fibers are dispensable for progression through the ongoing cell cycle.
Prevention of cell spreading or disruption of actin filaments inhibits growth factor stimulated cell cycle re-entry from quiescence, mainly because of a failure to induce cyclin D expression. Ectopic cyclin D expression overrules anchorage-dependency, suggesting that cell spreading per se is not required as long as cyclin D is otherwise induced. We investigated whether cyclin D expression in cells exiting mitosis is sufficient to drive morphology-independent cell cycle progression in continuously cycling (i.e. not quiescent) cells. Disruption of post-mitotic actin reorganization did not affect substratum reattachment but abolished the formation of filopodia, lamellipodia and ruffles, as well as stress fiber organization, focal adhesion assembly and cell spreading. Furthermore, integrin-mediated focal adhesion kinase (FAK) autophosphorylation and growth factor stimulated p42/p44 mitogen activated protein kinase (MAPK) activation were inhibited. Despite a progressive loss of cyclin D expression in late G1, cyclin E and cyclin A were normally induced. In addition, cells committed to DNA synthesis and completed their entire cycle. Our results demonstrate that post-mitotic disruption of the actin cytoskeleton allows cell cycle progression independent of focal adhesion signaling, cytoskeletal organization and cell shape, presumably because pre-existing cyclin D levels are sufficient to drive cell cycle progression at the M-G1 border.
Margadant
Coert
C
Cellular Architecture and Dynamics, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
van Opstal
Angelique
A
Boonstra
Johannes
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009447:Neuroblastoma; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism*
D000199:Actins; D056741:Cyclin D; D016213:Cyclins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3