Changes In Cell Shape And Anchorage In Relation To The Restriction Point

The restriction point (R) separates the G, phase of continuously cycling cells into two functionally different parts. The first part, G(1)-pm, represents the growth factor dependent post-mitotic interval from mitosis to R, which is of constant length (3-4 h). The second part, G(1)-ps, represents the growth factor independent, pre-S phase interval of G(1) that lasts from R to S and that varies in time from I to 10 h. G(1)-pm cells rapidly exit (within 1 h) from the cell cycle and enter G(0) as a response to serum withdrawal. The finding that R occurs at a set time after mitosis indicates that R may be related to the metabolic and/or structural changes that the cell underwent during the previous mitosis. We have recently shown that phosphorylation of the retinoblastorna tumor suppressor protein (pRb) is not the molecular mechanism behind R, as has been suggested previously. Here, we present an alternative explanation for R. In the present study, we applied a single cell approach using time-lapse analysis, which revealed that upon serum starvation the G(1)-pm cells rapidly underwent a transient change in cell shape from flat to spherical before exiting to Go. Platelet derived growth factor (PDGF) counteracted this change in shape and also prevented exit to Go to the same extent. Furthermore epidermal growth factor (EGF) and insulin like growth factor (IGF-1), which only partially counteracted this change, only partially counteracts exit to G(0). These data clearly indicate a direct link between change in cell shape and exit to G(0) in G(1)-cells that have not passed (C) 2004 Wiley-Liss, Inc.